Experimental approaches to assess melanocytes mosaicism in segmental vitiligo

array:23 ["pii" => "S0365059622002847" "issn" => "03650596" "doi" => "10.1016/j.abd.2022.05.001" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "677" "copyrightAnyo" => "2022" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by/4.0/" "subdocumento" => "fla" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "pt" => array:18 [ "pii" => "S2666275222002971" "issn" => "26662752" "doi" => "10.1016/j.abdp.2022.12.008" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "677" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by/4.0/" "subdocumento" => "fla" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "pt" => array:12 [ "idiomaDefecto" => true "cabecera" => "Artigo especial" "titulo" => "Abordagens experimentais para avaliar melanócitos em mosaico no vitiligo segmentar" "tienePdf" => "pt" "tieneTextoCompleto" => "pt" "tieneResumen" => "pt" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "216" "paginaFinal" => "220" ] ] "contieneResumen" => array:1 [ "pt" => true ] "contieneTextoCompleto" => array:1 [ "pt" => true ] "contienePdf" => array:1 [ "pt" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3138 "Ancho" => 3341 "Tamanyo" => 1105261 ] ] "descripcion" => array:1 [ "pt" => "Desenho experimental para testar a hipótese do mosaicismo no vitiligo segmentar. (A) Representação de paciente com vitiligo segmentar. Áreas hipocrômicas destacadas com um círculo vermelho completo seriam avaliadas quanto à presença de melanócitos em mosaico. Amostra de pele contralateral marcada com círculo pontilhado seria usada como controle interno. (B) Composição cutânea para pele contralateral e hipocrômica. A pele hipocrômica inclui melanócitos em mosaico residuais. (C) Técnica de bolhas de sucção subepidérmica de pele normal e afetada. A tripsinização do teto da bolha possibilita o desprendimento de queratinócitos e melanócitos, que podem estar junto com células imunoinfiltradas, utilizadas nos experimentos com células únicas. (D) Código de barras de célula única. O conjunto contendo a suspensão de células para a pele normal e afetada seria carregado no canal de célula única. Células individuais seriam incorporadas em gotículas de óleo e marcadas com esferas com código de barras exclusivos, o que possibilitaria a aplicação de diferentes conjuntos de abordagens de célula única, incluindo scWGS, scRNA e scATAC. (E) Cluster de células utilizando dados ômicos. A análise de clusters agruparia células que compartilham estados semelhantes e identificaria melanócitos em mosaico, bem como outros tipos de células incluídos no tecido da bolha." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Gerson Dellatorre, Vinicius M. Fava, Marcelo Távora Mira, Caio Cesar Silva de Castro" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Gerson" "apellidos" => "Dellatorre" ] 1 => array:2 [ "nombre" => "Vinicius M." "apellidos" => "Fava" ] 2 => array:2 [ "nombre" => "Marcelo Távora" "apellidos" => "Mira" ] 3 => array:2 [ "nombre" => "Caio Cesar" "apellidos" => "Silva de Castro" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0365059622002847" "doi" => "10.1016/j.abd.2022.05.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622002847?idApp=UINPBA00008Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222002971?idApp=UINPBA00008Z" "url" => "/26662752/0000009800000002/v1_202302281436/S2666275222002971/v1_202302281436/pt/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S0365059622002951" "issn" => "03650596" "doi" => "10.1016/j.abd.2022.05.002" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "688" "copyright" => "Sociedade Brasileira de Dermatologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by/4.0/" "subdocumento" => "crp" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "Letter - Research" "titulo" => "A retrospective study of oral tofacitinib therapy for alopecia areata" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "221" "paginaFinal" => "224" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1728 "Ancho" => 2750 "Tamanyo" => 226663 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Patient selection flowchart." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Xinaida Taligare Vasconcelos Lima, Melissa Bambery, Maria Beatrice Alora" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Xinaida Taligare Vasconcelos" "apellidos" => "Lima" ] 1 => array:2 [ "nombre" => "Melissa" "apellidos" => "Bambery" ] 2 => array:2 [ "nombre" => "Maria Beatrice" "apellidos" => "Alora" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S2666275222003058" "doi" => "10.1016/j.abdp.2022.12.016" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222003058?idApp=UINPBA00008Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622002951?idApp=UINPBA00008Z" "url" => "/03650596/0000009800000002/v1_202302171515/S0365059622002951/v1_202302171515/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0365059622002768" "issn" => "03650596" "doi" => "10.1016/j.abd.2022.03.006" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "669" "copyright" => "Sociedade Brasileira de Dermatologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by/4.0/" "subdocumento" => "fla" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Skin, mucosa and nail findings in hospitalized pediatric patients with Coronavirus disease-2019 (COVID-19)" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "208" "paginaFinal" => "215" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1639 "Ancho" => 3341 "Tamanyo" => 492686 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Some of the mucosa, nail and hair findings of the study group." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Tunç Özen, Filiz Cebeci Kahraman, Sevliya Öcal, Hüsnü Fahri Ovalı" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Tunç" "apellidos" => "Özen" ] 1 => array:2 [ "nombre" => "Filiz Cebeci" "apellidos" => "Kahraman" ] 2 => array:2 [ "nombre" => "Sevliya" "apellidos" => "Öcal" ] 3 => array:2 [ "nombre" => "Hüsnü Fahri" "apellidos" => "Ovalı" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S2666275222002880" "doi" => "10.1016/j.abdp.2022.11.033" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222002880?idApp=UINPBA00008Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622002768?idApp=UINPBA00008Z" "url" => "/03650596/0000009800000002/v1_202302171515/S0365059622002768/v1_202302171515/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Special Article" "titulo" => "Experimental approaches to assess melanocytes mosaicism in segmental vitiligo" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "216" "paginaFinal" => "220" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Gerson Dellatorre, Vinicius M. Fava, Marcelo Távora Mira, Caio Cesar Silva de Castro" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Gerson" "apellidos" => "Dellatorre" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Vinicius M." "apellidos" => "Fava" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Marcelo Távora" "apellidos" => "Mira" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 3 => array:4 [ "nombre" => "Caio Cesar" "apellidos" => "Silva de Castro" "email" => array:1 [ 0 => "caio.castro@pucpr.br" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Santa Casa de Misericórdia Hospital, Curitiba, PR, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Infectious Diseases and Immunity in Global Health Program, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3138 "Ancho" => 3341 "Tamanyo" => 1107930 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Experimental design to test the mosaicism hypothesis in segmental vitiligo. (A) Depiction of a segmental vitiligo patient. Hypochromic areas highlighted with a full red circle would be evaluated for the presence of mosaic melanocytes. A contralateral skin sample marked with a dotted circle would be used as an internal control. (B) Skin composition for contralateral and hypochromic skin. The hypochromic skin includes residual mosaic melanocytes. (C) Subepidermal suction blister technique of normal and affected skin. The trypsinization of the blister’s roof allows the detachment of keratinocytes and melanocytes that can be together with immune infiltrated cells used in the single-cell experiments. (D) Single-cell barcoding. The pool containing cell suspension for normal and affected skin would be loaded to the single-cell channel. Individual cells would be incorporated into oil droplets and marked with unique barcoded beads, which would allow the application of different sets of single-cell approaches including scWGS, scRNA, and scATAC. (E) Cell clustering using omics data. Clustering analysis would group cells sharing similar states and identify mosaic melanocytes as well as other cell types included in the blister extract." ] ] ] "textoCompleto" => "IntroductionAccording to an international consensus, vitiligo is classified into three main groups: Segmental (SV), Non-Segmental (NSV), and mixed vitiligo (coexistence of SV and NSV).<a class="elsevierStyleCrossRef" href="#bib0005">1</a> The consensus describes SV as a depigmentation spreading within a segment, uni-, bi-, or pluri-segmental, however, this distribution can occasionally be bilateral.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a> The segmental distribution pattern is not the only difference between SV and NSV (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The median age of SV onset is 16 years, on average 8 to 10 years earlier than the median age of NSV onset.<a class="elsevierStyleCrossRefs" href="#bib0015">3–5</a> Additionally, depigmentation in SV typically has a rapid progression with a limited-time course between 6 to 24 months, rarely extending after this period, while NSV is chronic with an uncertain lifelong time course.<a class="elsevierStyleCrossRefs" href="#bib0005">1,6</a> In contrast to NSV, SV presents early involvement of hair follicles melanocytes, with up to 50% of SV patients exhibiting poliosis in the affected area.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> The prevalence of concomitant autoimmune disorders (e.g., thyroiditis) is lower in SV.<a class="elsevierStyleCrossRefs" href="#bib0015">3,7</a> SV and NSV also differ regarding response to treatment: in general, SV patients have a poor response to phototherapy compared to NSV, possibly due to earlier depletion of follicular reservoir in the former.<a class="elsevierStyleCrossRefs" href="#bib0040">8,9</a> Conversely, SV patients have an excellent and long-term response to surgical interventions such as melanocyte-keratinocyte transplant.<a class="elsevierStyleCrossRefs" href="#bib0050">10,11</a> The long-term success of transplant therapy in SV suggests a confined defect of melanocyte–keratinocyte metabolism.<a class="elsevierStyleCrossRef" href="#bib0050">10</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Reports suggest differences in the biological mechanisms underlying the pathogenesis of SV as compared to NSV. For example, serum levels of TWEAK (Tumor Necrosis Factor-like Weak inducer of Apoptosis) were significantly higher in SV compared to NSV patients.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> Moreover, TWEAK was shown as a biomarker with 100% sensitivity and 80.1% specificity in differentiating SV from NSV.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> In contrast to NSV, systemic oxidative stress has a weak and limited contribution to SV pathogenesis.<a class="elsevierStyleCrossRefs" href="#bib0065">13,14</a> In SV, a significant increase of stress-induced markers (e.g., mitochondrial, HSP70 and CXCL16) was observed only in perilesional skin suggesting a localized pathogenic mechanism promoting depigmentation. Immunophenotypic analysis of circulating immune cells of SV patients identified unaltered regulatory T-cells (Tregs) compared to healthy controls while NSV patients had decreased levels of Tregs.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Collectively, multiple pieces of evidence indicate unaltered systemic immunity in SV patients and point to a localized cytotoxic reaction targeting epidermal melanocytes.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Taken together, these differences and the remarkable similarity of SV distribution pattern to mosaic melanocyte diseases (as segmental lentiginose and verrucous epidermal nevus) led us to hypothesize the involvement of somatic mosaicism in SV pathogenesis.<a class="elsevierStyleCrossRefs" href="#bib0080">16,17</a>How to test the hypothesisMosaicism designates individuals encompassing at least two cell populations derived from a single zygote but with distinct genotype or epigenetic profiles.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> The phenotypic presentation of a disease caused by genetic mosaicism is conditional to the type of variation and phase of development that a somatic mutation that occurred.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Variants leading to genetic mosaicism range from chromosomal duplications, segment translocations, copy number variation (CNV), single-nucleotide variants (SNV), or epigenetic changes such as transcriptomic alterations caused by retrotransposition insertions. The embryonic phase and cell differentiation status where a de novo mutation or retrotransposition occurred delineates the extent of tissues/cells involved in the mosaicism. The hypothesis to be tested suggest that genetic mosaicism in SV occurred at some point during skin/melanocyte differentiation. Different approaches can be applied to test the mosaicism hypothesis in SV, each aiming to detect a distinct type of mosaicism. Here we proposed examples by adapting designs applied to study the host response to infections, detect somatic mutations in cancers and evaluate embryonic development.<a class="elsevierStyleCrossRefs" href="#bib0100">20–23</a>Paired contrast of perilesional skin and contralateral healthy skin in SVThe detection of mosaicism in human diseases can be challenging as the number of mosaic cells within the targeted tissue might be small. In addition, mosaic melanocytes would likely be absent inside existing SV lesions as a loss of melanocytes is the cause of vitiligo. Therefore, high-resolution methods at the single-cell level may be required to detect underrepresented cell populations.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> To detect potential mosaic cells, evaluating tissue obtained from hypochromic skin regions from individuals at the earliest stage of SV would be required (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). An advantage of studying the mosaicism hypothesis in SV is the possibility to use internal controls since SV is usually constrained to a unilateral segment: if the de novo mutation occurred during skin differentiation in one segment, a contralateral healthy skin could be used to establish the melanocyte’s “normal” profile (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). This strategy would allow controlling for confounding effects caused by interindividual variability when combining multiple SV cases.<a class="elsevierStyleCrossRef" href="#bib0125">25</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Target tissue preparationMelanocytes account for ∼2.8% of the cell population in the epidermis and approximately 1200 melanocytes exist per mm2 of the skin independently of an individual ethnicity (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B).<a class="elsevierStyleCrossRef" href="#bib0130">26</a> To capture a representative number of viable mosaic melanocytes for the single-cell analysis, hypochromic areas of early-onset active SV would need to be determined using Wood’s lamp. Keratinocyte-melanocyte sampling of these areas could be performed with a suction blister epidermal grafting technique with subsequent trypsinization of the blister’s roof to detach the cells into a suspension (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C).<a class="elsevierStyleCrossRef" href="#bib0135">27</a> An advantage of collecting epidermis by using the suction blister is the widening of the sampled area, which increases the likelihood of capturing remaining viable mosaic melanocytes while being nearly a scarless technique, which facilitates patient inclusion.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> To evaluate follicular melanoblasts not captured by the blister method, a punch technique could also be used. A punch biopsy is more invasive than blistering and the overall proportion of melanoblasts captured would be small. However, methodological refinements of single cell analysis could allow in a near future the study of smaller cell populations.Identifying mosaic cells in segmental vitiligo via genetic and epigenetic variationsTo evaluate the presence of mosaic melanocytes, fluorescence-activated cell sorting selection could be used to separate the melanocyte fraction of blister extracts or melanoblasts from punch biopsies. Next, whole genome sequencing (WGS) would be performed using DNA extracted from melanocytes from hypochromic and contralateral skin from the same individuals. Variants detected in contralateral tissues would be used to exclude germline variants. Algorithms designed to detect tumor cells, such as MuTect2,<a class="elsevierStyleCrossRef" href="#bib0145">29</a> or specific for mosaic cells, such as MosaicForecast<a class="elsevierStyleCrossRef" href="#bib0150">30</a> and DeepMosaic,<a class="elsevierStyleCrossRef" href="#bib0155">31</a> could be used to detect somatic mutations. The limitation of the bulk approach is the inability to separate mosaic cells from regular melanocytes and evaluate their interaction with other cells. Addressing this limitation would require single-cell (sc) sequencing technologies evaluating either the transcriptomic, epigenetic, or DNA sequence profile of individual cells (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>D).<a class="elsevierStyleCrossRef" href="#bib0160">32</a> scWGS allows the evaluation of structural variation, CNVs, and SNVs in individual cells. A high throughput scWGS method developed to detect subclonal mutations in cancer could be used to test the hypothesis of melanocyte mosaicism.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> In SV, mosaic cells would share a state (i.e., specific genetic variants) that could be used to merge cells in clusters and define the proportion and the type of genetic variants present in mosaic cells (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>E).<a class="elsevierStyleCrossRef" href="#bib0165">33</a> Epigenetic mosaicism in SV could be tested by using a multi-omics approach with transcriptomic (scRNA) and chromatin accessibility (scATAC) measures. Multi-omics approaches are currently being used to study a diverse set of diseases.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> Analyses of scRNA and scATAC could be used to identify mosaic cells via transcriptomic and epigenomic similarities with tools such as Seurat,<a class="elsevierStyleCrossRef" href="#bib0175">35</a> Monocle,<a class="elsevierStyleCrossRef" href="#bib0180">36</a> and Cicero.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> A similar scRNA approach applied to study human embryos was able to successfully detect mosaicism.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> An advantage of the single cell compared to bulk approaches is the ability to study the relationship between cells present in the blister extract or punch biopsies. In fact, scRNA study of blistering extracts has shown the recovery of melanocytes from NSV lesions.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> Applying a single-cell approach to study SV could test the mosaicism hypothesis while assessing the local immune profile as shown for NSV.<a class="elsevierStyleCrossRef" href="#bib0120">24</a>Financial supportNone declared.Authors’ contributionsGerson Dellatorre: Study concept, writing and approval of the final manuscript.Vinicius Medeiros Fava: Study concept, writing and approval of the final manuscript.Marcelo Távora Mira: Writing and approval of the final manuscript.Caio Cesar Silva de Castro: Study concept, writing and approval of the final manuscript.Conflicts of interestNone declared." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1851029" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1609543" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "How to test the hypothesis" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Paired contrast of perilesional skin and contralateral healthy skin in SV" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Target tissue preparation" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Identifying mosaic cells in segmental vitiligo via genetic and epigenetic variations" ] ] ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "Financial support" ] 5 => array:2 [ "identificador" => "sec0035" "titulo" => "Authors’ contributions" ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-03-16" "fechaAceptado" => "2022-05-26" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1609543" "palabras" => array:3 [ 0 => "Genetics" 1 => "Mosaicism" 2 => "Vitiligo" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Vitiligo is an autoimmune disease of the skin that results in localized or disseminated white macules. One common feature of several existing classification protocols is the distribution of the disease into two main subtypes, non-segmental vitiligo (NSV) and segmental vitiligo (SV). SV is characterized by depigmentation spreading within one or more skin segments while NSV is widespread. Several clinical-epidemiological observations suggest that SV has distinct autoimmune pathophysiology compared to NSV. Furthermore, the clinical distribution pattern of SV lesions closely resembles other melanocyte mosaicism diseases. These observations led us to hypothesize that SV is caused by a localized autoimmune reaction targeting epidermal mosaicism melanocytes. Here, we proposed examples of experimental approaches to assess mosaicism in SV patients." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Study conducted at the Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3138 "Ancho" => 3341 "Tamanyo" => 1107930 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Experimental design to test the mosaicism hypothesis in segmental vitiligo. (A) Depiction of a segmental vitiligo patient. Hypochromic areas highlighted with a full red circle would be evaluated for the presence of mosaic melanocytes. A contralateral skin sample marked with a dotted circle would be used as an internal control. (B) Skin composition for contralateral and hypochromic skin. The hypochromic skin includes residual mosaic melanocytes. (C) Subepidermal suction blister technique of normal and affected skin. The trypsinization of the blister’s roof allows the detachment of keratinocytes and melanocytes that can be together with immune infiltrated cells used in the single-cell experiments. (D) Single-cell barcoding. The pool containing cell suspension for normal and affected skin would be loaded to the single-cell channel. Individual cells would be incorporated into oil droplets and marked with unique barcoded beads, which would allow the application of different sets of single-cell approaches including scWGS, scRNA, and scATAC. (E) Cell clustering using omics data. Clustering analysis would group cells sharing similar states and identify mosaic melanocytes as well as other cell types included in the blister extract." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Segmental \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-segmental \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median age of onset \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Earlier onset \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Later onset \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Association with autoimmune diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Less frequent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequent \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Role of early involvement of oxidative Stress \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Present \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical Manifestation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Segmental, unilateral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Varied \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Course \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Short and limited \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic and unstable \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum TWEAK levels \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Higher \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lower \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tregs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unaffected \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diminished \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Melanocyte depletion at the follicle (polyosis) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Less frequent \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Response to clinical therapies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Poor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mod / Good \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Long-term response to melanocyte-keratinocyte transplant procedure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Better \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Worse \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of segmental and non-segmental vitiligo." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:37 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Revised classification/nomenclature of vitiligo and related issues: the Vitiligo Global Issues Consensus Conference" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Ezzedine" 1 => "H.W. Lim" 2 => "T. Suzuki" 3 => "I. Katayama" 4 => "I. Hamzavi" 5 => "C.C.E. Lan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jpy.13323" "Revista" => array:6 [ "tituloSerie" => "Pigment Cell & Melanoma Research" "fecha" => "2012" "volumen" => "25" "paginaInicial" => "E1" "paginaFinal" => "13" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36798977" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association between bilateral segmental vitiligo and lichen striatus: an expression of mosaicism?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L.D. Correia" 1 => "C.C.S. Castro" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Int J Dermatol" "fecha" => "2018" "volumen" => "57" "paginaInicial" => "992" "paginaFinal" => "993" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A pattern of association between clinical form of vitiligo and disease-related variables in a Brazilian population" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C.C.S. Castro" 1 => "L.M. Nascimento" 2 => "M. Olandoski" 3 => "M.T. Mira" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jdermsci.2011.09.011" "Revista" => array:6 [ "tituloSerie" => "J Dermatol Sci" "fecha" => "2012" "volumen" => "65" "paginaInicial" => "63" "paginaFinal" => "67" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22030153" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Jin" 1 => "G.H.L. Roberts" 2 => "T.M. Ferrara" 3 => "S. Ben" 4 => "N. van Geel" 5 => "A. Wolkerstorfer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41467-019-08337-4" "Revista" => array:5 [ "tituloSerie" => "Nat Commun" "fecha" => "2019" "volumen" => "10" "paginaInicial" => "391" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30674883" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Segmental vitiligo: clinical findings in 208 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.K. Hann" 1 => "H.J. Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0190-9622(96)90718-5" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "1996" "volumen" => "35" "paginaInicial" => "671" "paginaFinal" => "674" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8912558" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitiligo" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K. Ezzedine" 1 => "V. Eleftheriadou" 2 => "M. Whitton" 3 => "N. van Geel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(14)60763-7" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2015" "volumen" => "386" "paginaInicial" => "74" "paginaFinal" => "84" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25596811" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comorbid autoimmune diseases in patients with vitiligo: A cross-sectional study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L. Gill" 1 => "A. Zarbo" 2 => "P. Isedeh" 3 => "G. Jacobsen" 4 => "H.W. Lim" 5 => "I. Hamzavi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2015.08.063" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2016" "volumen" => "74" "paginaInicial" => "295" "paginaFinal" => "302" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26518171" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation of the effects of NB-UVB in both segmental and non-segmental vitiligo affecting different body sites" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "T.S. Anbar" 1 => "W. Westerhof" 2 => "A.T. Abdel-Rahman" 3 => "M.A. El-Khayyat" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Photodermatol Photoimmunol Photomed" "fecha" => "2006" "volumen" => "22" "paginaInicial" => "157" "paginaFinal" => "163" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Excimer light photototherapy of segmental and non-segmental vitiligo: experience in Taiwan" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Y.P. Cheng" 1 => "H.Y. Chiu" 2 => "S.H. Jee" 3 => "T.F. Tsai" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1600-0781.2011.00628.x" "Revista" => array:6 [ "tituloSerie" => "Photodermatol Photoimmunol Photomed" "fecha" => "2012" "volumen" => "28" "paginaInicial" => "6" "paginaFinal" => "11" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22211997" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term follow-up of patients undergoing autologous noncultured melanocyte-keratinocyte transplantation for vitiligo and other leukodermas" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Silpa-Archa" 1 => "J.L. Griffth" 2 => "R.H. Huggins" 3 => "M.D. Henderson" 4 => "H.A. Kerr" 5 => "G. Jacobsen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2017.01.056" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2017" "volumen" => "77" "paginaInicial" => "318" "paginaFinal" => "327" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28502377" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Six-year follow-up of vitiligo patients successfully treated with autologous non-cultured melanocyte-keratinocyte transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Altalhab" 1 => "M.I. AlJasser" 2 => "S.V. Mulekar" 3 => "A.A. Issa" 4 => "S. Mulekar" 5 => "J. Diaz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jdv.15411" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol." "fecha" => "2019" "volumen" => "33" "paginaInicial" => "1172" "paginaFinal" => "1176" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30793805" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum TWEAK: A cutoff between segmental and nonsegmental vitiligo" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.E.A.I. El-Taweel" 1 => "A.M.N. Abdelrahman" 2 => "S. Sabry" 3 => "R.M. Salem" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jocd.13644" "Revista" => array:6 [ "tituloSerie" => "J Cosmet Dermatol" "fecha" => "2021" "volumen" => "20" "paginaInicial" => "1017" "paginaFinal" => "1021" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32808442" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "RIP1-Mediated Necroptosis Facilitates Oxidative StressInduced Melanocyte Death, Offering Insight into Vitiligo" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Li" 1 => "X. Yi" 2 => "T. Zhuang" 3 => "S. Zhang" 4 => "S. Li" 5 => "Y. Yang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jid.2020.06.042" "Revista" => array:6 [ "tituloSerie" => "J Invest Dermatol" "fecha" => "2021" "volumen" => "141" "paginaInicial" => "2921" "paginaFinal" => "2931" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34102211" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Basic evidence for epidermal H2O2/ONOO(-) ‒ mediated oxidation/nitration in segmental vitiligo is supported by repigmentation of skin and eyelashes after reduction of epidermal H2O2 with topical NB-UVB-activated pseudocatalase PC-KUS" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.U. Schallreuter" 1 => "M.A.E.L. Salem" 2 => "S. Holtz" 3 => "A. Panske" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1096/fj.12-226779" "Revista" => array:6 [ "tituloSerie" => "FASEB J" "fecha" => "2013" "volumen" => "27" "paginaInicial" => "3113" "paginaFinal" => "3122" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23629861" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunophenotypic analysis reveals differences in circulating immune cells in peripheral blood of segmental and non-segmental vitiligo patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Willemsen" 1 => "N.F. Post" 2 => "N.O.P. van Uden" 3 => "V.S. Narayan" 4 => "S. Chielie" 5 => "E.H. Kemp" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "J Invest Dermatol" "fecha" => "2022" "volumen" => "142" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Segmental vitiligo as the possible expression of cutaneous somatic mosaicism: implications for common non-segmental vitiligo" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Taïeb" 1 => "F. Morice-Picard" 2 => "T. Jouary" 3 => "K. Ezzedine" 4 => "M. Cario-André" 5 => "Y. Gauthier" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Pigment Cell & Melanoma Research" "fecha" => "2008" "volumen" => "21" "paginaInicial" => "646" "paginaFinal" => "652" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The distribution pattern of segmental vitiligo: clues for somatic mosaicism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. van Geel" 1 => "R. Speeckaert" 2 => "E. Melsens" 3 => "S.P. Toelle" 4 => "M. Speeckaert" 5 => "S. De Schepper" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjd.12013" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2013" "volumen" => "168" "paginaInicial" => "56" "paginaFinal" => "64" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22913564" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A six-attribute classification of genetic mosaicism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Martinez-Glez" 1 => "J. Tenorio" 2 => "J. Nevado" 3 => "G. Gordo" 4 => "L. Rodríguez-Laguna" 5 => "M. Feito" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41436-020-0877-3" "Revista" => array:6 [ "tituloSerie" => "Genet Med" "fecha" => "2020" "volumen" => "22" "paginaInicial" => "1743" "paginaFinal" => "1757" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32661356" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A genomic view of mosaicism and human disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L.G. Biesecker" 1 => "N.B. Spinner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrg3424" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Genet" "fecha" => "2013" "volumen" => "14" "paginaInicial" => "307" "paginaFinal" => "320" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23594909" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Single-cell analysis of human embryos reveals diverse patterns of aneuploidy and mosaicism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.R. Starostik" 1 => "O.A. Sosina" 2 => "R.C. McCoy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1101/gr.262774.120" "Revista" => array:6 [ "tituloSerie" => "Genome Res" "fecha" => "2020" "volumen" => "30" "paginaInicial" => "814" "paginaFinal" => "825" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32641298" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of somatic mutations in single cell DNA-seq using a spatial model of allelic imbalance" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "L.J. Luquette" 1 => "C.L. Bohrson" 2 => "M.A. Sherman" 3 => "P.J. Park" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Nat Commum" "fecha" => "2019" "volumen" => "10" "paginaInicial" => "3908" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Laks" 1 => "A. McPherson" 2 => "H. Zahn" 3 => "D. Lai" 4 => "A. Steif" 5 => "J. Brimhall" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Cell" "fecha" => "2019" "volumen" => "179" "itemHostRev" => array:3 [ "pii" => "S0002937815006699" "estado" => "S300" "issn" => "00029378" ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A system biology approach identifies candidate drugs to reduce mortality in severely ill patients with COVID-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V.M. Fava" 1 => "M. Bourgey" 2 => "P.M. Nawarathna" 3 => "M. Orlova" 4 => "P. Cassart" 5 => "D.C. Vinh" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Sci Adv." "fecha" => "2022" "volumen" => "8" "paginaInicial" => "eabm2510" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in Treg function" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.J. Gellatly" 1 => "J.P. Strassner" 2 => "K. Essien" 3 => "M.A. Refat" 4 => "R.L. Murphy" 5 => "A. Coffin-Schmitt" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Sci Transl Med" "fecha" => "2021" "volumen" => "13" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alveolar macrophages from persons living with HIV show impaired epigenetic response to Mycobacterium tuberculosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W. Correa-Macedo" 1 => "V.M. Fava" 2 => "M. Orlova" 3 => "P. Cassart" 4 => "R. Olivenstein" 5 => "J. Sanz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Clin Invest" "fecha" => "2021" "volumen" => "131" "paginaInicial" => "e148013" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Skin melanocytes: biology and development" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Cichorek" 1 => "M. Wachulska" 2 => "A. Stasiewicz" 3 => "A. Tyminska" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5114/pdia.2013.33376" "Revista" => array:6 [ "tituloSerie" => "Postepy Dermatol Alergol" "fecha" => "2013" "volumen" => "30" "paginaInicial" => "30" "paginaFinal" => "41" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24278043" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Noncultured epidermal suspension grafting using suction blisters as donor tissue for vitiligo" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Tovar-Garza" 1 => "J.A. Hinojosa" 2 => "L.S. Hynan" 3 => "A.G. Pandya" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2018.10.041" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2019" "volumen" => "80" "paginaInicial" => "1152" "paginaFinal" => "1154" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30393095" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Optimizing suction blister epidermal graft technique in the surgical treatment of vitiligo" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Dellatorre" 1 => "W. Bertolini" 2 => "C.C.S. Castro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1590/abd1806-4841.20176332" "Revista" => array:6 [ "tituloSerie" => "An Bras Dermatol" "fecha" => "2017" "volumen" => "92" "paginaInicial" => "888" "paginaFinal" => "890" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29364459" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Calling Somatic SNVs and Indels with Mutect2" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D. Benjamin" 1 => "T. Sato" 2 => "K. Cibulskis" 3 => "G. Getz" 4 => "C. Stewart" 5 => "L. Linchtenstein" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "bioRxiv" "fecha" => "2019" "paginaInicial" => "1" "paginaFinal" => "8" ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Accurate detection of mosaic variants in sequencing data without matched controls" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Dou" 1 => "M. Kwon" 2 => "R.E. Rodin" 3 => "I. Cortés-Ciriano" 4 => "R. Doan" 5 => "L.J. Luquette" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41587-019-0368-8" "Revista" => array:6 [ "tituloSerie" => "Nature biotechnology" "fecha" => "2020" "volumen" => "38" "paginaInicial" => "314" "paginaFinal" => "319" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31907404" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "DeepMosaic: Control-independent mosaic single nucleotide variant detection using deep convolutional neural networks" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "X. Yang" 1 => "X. Xu" 2 => "M.W. Breuss" 3 => "D. Antaki" 4 => "L.L. Ball" 5 => "C. Chung" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "bioRxiv" "fecha" => "2021" "paginaInicial" => "1" "paginaFinal" => "38" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Single-cell analysis enters the multiomics age" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.M. Perkel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Nature" "fecha" => "2021" "volumen" => "595" "paginaInicial" => "614" "paginaFinal" => "616" ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comprehensive Integration of Single-Cell Data" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Stuart" 1 => "A. Butler" 2 => "P. Hoffman" 3 => "C. Hafemeister" 4 => "E. Papalexi" 5 => "W.M. Mauck 3rd" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Cell" "fecha" => "2019" "volumen" => "177" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multi-omics approaches to disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Y. Hasin" 1 => "M. Seldin" 2 => "A. Lusis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13059-017-1215-1" "Revista" => array:5 [ "tituloSerie" => "Genome Biol" "fecha" => "2017" "volumen" => "18" "paginaInicial" => "83" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28476144" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Integrated analysis of multimodal single-cell data" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Hao" 1 => "S. Hao" 2 => "E. Andersen-N" 3 => "W.M. Mauck 3rd" 4 => "S. Zheng" 5 => "A. Butler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cell.2021.04.048" "Revista" => array:6 [ "tituloSerie" => "Cell" "fecha" => "2021" "volumen" => "184" "paginaInicial" => "3573" "paginaFinal" => "3587" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34062119" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The single-cell transcriptional landscape of mammalian organogenesis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Cao" 1 => "M. Spielmann" 2 => "X. Qiu" 3 => "X. Huang" 4 => "D.M. Ibrahim" 5 => "A.J. Hill" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41586-019-0969-x" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2019" "volumen" => "566" "paginaInicial" => "496" "paginaFinal" => "502" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30787437" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.A. Pliner" 1 => "J.S. Packer" 2 => "J.L. McFaline-Figueroa" 3 => "D.A. Cusanovich" 4 => "R.M. Daza" 5 => "D. Aghamirzaie" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Mol Cell" "fecha" => "2018" "volumen" => "71" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/03650596/0000009800000002/v1_202302171515/S0365059622002847/v1_202302171515/en/main.assets" "Apartado" => array:4 [ "identificador" => "87261" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Special Article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03650596/0000009800000002/v1_202302171515/S0365059622002847/v1_202302171515/en/main.pdf?idApp=UINPBA00008Z&text.app=https://clinics.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622002847?idApp=UINPBA00008Z"]

Statistics

Special Article

Experimental approaches to assess melanocytes mosaicism in segmental vitiligo

Gerson Dellatorrea, Vinicius M. Favab, Marcelo Távora Miraa,c,d, Caio Cesar Silva de Castroa,e,

Corresponding author

caio.castro@pucpr.br

Corresponding author.

a Santa Casa de Misericórdia Hospital, Curitiba, PR, Brazil

b Infectious Diseases and Immunity in Global Health Program, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada

c Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil

d School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil

e School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil

Read

4191

Times
was read the article

1569

Total PDF

2622

Total HTML

Share statistics

 array:23 [
  "pii" => "S0365059622002847"
  "issn" => "03650596"
  "doi" => "10.1016/j.abd.2022.05.001"
  "estado" => "S300"
  "fechaPublicacion" => "2023-03-01"
  "aid" => "677"
  "copyrightAnyo" => "2022"
  "documento" => "article"
  "crossmark" => 1
  "licencia" => "http://creativecommons.org/licenses/by/4.0/"
  "subdocumento" => "fla"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "pt" => array:18 [
      "pii" => "S2666275222002971"
      "issn" => "26662752"
      "doi" => "10.1016/j.abdp.2022.12.008"
      "estado" => "S300"
      "fechaPublicacion" => "2023-03-01"
      "aid" => "677"
      "documento" => "article"
      "crossmark" => 1
      "licencia" => "http://creativecommons.org/licenses/by/4.0/"
      "subdocumento" => "fla"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:1 [
        "total" => 0
      ]
      "pt" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Artigo especial</span>"
        "titulo" => "Abordagens experimentais para avaliar melan&#243;citos em mosaico no vitiligo segmentar"
        "tienePdf" => "pt"
        "tieneTextoCompleto" => "pt"
        "tieneResumen" => "pt"
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "216"
            "paginaFinal" => "220"
          ]
        ]
        "contieneResumen" => array:1 [
          "pt" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "pt" => true
        ]
        "contienePdf" => array:1 [
          "pt" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0005"
            "etiqueta" => "Figura 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 3138
                "Ancho" => 3341
                "Tamanyo" => 1105261
              ]
            ]
            "descripcion" => array:1 [
              "pt" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Desenho experimental para testar a hip&#243;tese do mosaicismo no vitiligo segmentar&#46;</span> &#40;A&#41; Representa&#231;&#227;o de paciente com vitiligo segmentar&#46; &#193;reas hipocr&#244;micas destacadas com um c&#237;rculo vermelho completo seriam avaliadas quanto &#224; presen&#231;a de melan&#243;citos em mosaico&#46; Amostra de pele contralateral marcada com c&#237;rculo pontilhado seria usada como controle interno&#46; &#40;B&#41; Composi&#231;&#227;o cut&#226;nea para pele contralateral e hipocr&#244;mica&#46; A pele hipocr&#244;mica inclui melan&#243;citos em mosaico residuais&#46; &#40;C&#41; T&#233;cnica de bolhas de suc&#231;&#227;o subepid&#233;rmica de pele normal e afetada&#46; A tripsiniza&#231;&#227;o do teto da bolha possibilita o desprendimento de queratin&#243;citos e melan&#243;citos&#44; que podem estar junto com c&#233;lulas imunoinfiltradas&#44; utilizadas nos experimentos com c&#233;lulas &#250;nicas&#46; &#40;D&#41; C&#243;digo de barras de c&#233;lula &#250;nica&#46; O conjunto contendo a suspens&#227;o de c&#233;lulas para a pele normal e afetada seria carregado no canal de c&#233;lula &#250;nica&#46; C&#233;lulas individuais seriam incorporadas em got&#237;culas de &#243;leo e marcadas com esferas com c&#243;digo de barras exclusivos&#44; o que possibilitaria a aplica&#231;&#227;o de diferentes conjuntos de abordagens de c&#233;lula &#250;nica&#44; incluindo scWGS&#44; scRNA e scATAC&#46; &#40;E&#41; <span class="elsevierStyleItalic">Cluster</span> de c&#233;lulas utilizando dados &#244;micos&#46; A an&#225;lise de <span class="elsevierStyleItalic">clusters</span> agruparia c&#233;lulas que compartilham estados semelhantes e identificaria melan&#243;citos em mosaico&#44; bem como outros tipos de c&#233;lulas inclu&#237;dos no tecido da bolha&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Gerson Dellatorre, Vinicius M&#46; Fava, Marcelo T&#225;vora Mira, Caio Cesar Silva de Castro"
            "autores" => array:4 [
              0 => array:2 [
                "nombre" => "Gerson"
                "apellidos" => "Dellatorre"
              ]
              1 => array:2 [
                "nombre" => "Vinicius M&#46;"
                "apellidos" => "Fava"
              ]
              2 => array:2 [
                "nombre" => "Marcelo T&#225;vora"
                "apellidos" => "Mira"
              ]
              3 => array:2 [
                "nombre" => "Caio Cesar"
                "apellidos" => "Silva de Castro"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "pt"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S0365059622002847"
          "doi" => "10.1016/j.abd.2022.05.001"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622002847?idApp=UINPBA00008Z"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222002971?idApp=UINPBA00008Z"
      "url" => "/26662752/0000009800000002/v1_202302281436/S2666275222002971/v1_202302281436/pt/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S0365059622002951"
    "issn" => "03650596"
    "doi" => "10.1016/j.abd.2022.05.002"
    "estado" => "S300"
    "fechaPublicacion" => "2023-03-01"
    "aid" => "688"
    "copyright" => "Sociedade Brasileira de Dermatologia"
    "documento" => "simple-article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "crp"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Letter - Research</span>"
      "titulo" => "A retrospective study of oral tofacitinib therapy for alopecia areata"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "221"
          "paginaFinal" => "224"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1728
              "Ancho" => 2750
              "Tamanyo" => 226663
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0005"
              "detalle" => "Figure "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patient selection flowchart&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Xinaida Taligare Vasconcelos Lima, Melissa Bambery, Maria Beatrice Alora"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Xinaida Taligare Vasconcelos"
              "apellidos" => "Lima"
            ]
            1 => array:2 [
              "nombre" => "Melissa"
              "apellidos" => "Bambery"
            ]
            2 => array:2 [
              "nombre" => "Maria Beatrice"
              "apellidos" => "Alora"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "pt" => array:9 [
        "pii" => "S2666275222003058"
        "doi" => "10.1016/j.abdp.2022.12.016"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "pt"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222003058?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622002951?idApp=UINPBA00008Z"
    "url" => "/03650596/0000009800000002/v1_202302171515/S0365059622002951/v1_202302171515/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S0365059622002768"
    "issn" => "03650596"
    "doi" => "10.1016/j.abd.2022.03.006"
    "estado" => "S300"
    "fechaPublicacion" => "2023-03-01"
    "aid" => "669"
    "copyright" => "Sociedade Brasileira de Dermatologia"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "fla"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
      "titulo" => "Skin&#44; mucosa and nail findings in hospitalized pediatric patients with Coronavirus disease-2019 &#40;COVID-19&#41;"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "208"
          "paginaFinal" => "215"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0010"
          "etiqueta" => "Figure 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1639
              "Ancho" => 3341
              "Tamanyo" => 492686
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0010"
              "detalle" => "Figure "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Some of the mucosa&#44; nail and hair findings of the study group&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Tun&#231; &#214;zen, Filiz Cebeci Kahraman, Sevliya &#214;cal, H&#252;sn&#252; Fahri Oval&#305;"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Tun&#231;"
              "apellidos" => "&#214;zen"
            ]
            1 => array:2 [
              "nombre" => "Filiz Cebeci"
              "apellidos" => "Kahraman"
            ]
            2 => array:2 [
              "nombre" => "Sevliya"
              "apellidos" => "&#214;cal"
            ]
            3 => array:2 [
              "nombre" => "H&#252;sn&#252; Fahri"
              "apellidos" => "Oval&#305;"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "pt" => array:9 [
        "pii" => "S2666275222002880"
        "doi" => "10.1016/j.abdp.2022.11.033"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "pt"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222002880?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622002768?idApp=UINPBA00008Z"
    "url" => "/03650596/0000009800000002/v1_202302171515/S0365059622002768/v1_202302171515/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Special Article</span>"
    "titulo" => "Experimental approaches to assess melanocytes mosaicism in segmental vitiligo"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "216"
        "paginaFinal" => "220"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Gerson Dellatorre, Vinicius M&#46; Fava, Marcelo T&#225;vora Mira, Caio Cesar Silva de Castro"
        "autores" => array:4 [
          0 => array:3 [
            "nombre" => "Gerson"
            "apellidos" => "Dellatorre"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Vinicius M&#46;"
            "apellidos" => "Fava"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Marcelo T&#225;vora"
            "apellidos" => "Mira"
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          3 => array:4 [
            "nombre" => "Caio Cesar"
            "apellidos" => "Silva de Castro"
            "email" => array:1 [
              0 => "caio.castro@pucpr.br"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:5 [
          0 => array:3 [
            "entidad" => "Santa Casa de Miseric&#243;rdia Hospital&#44; Curitiba&#44; PR&#44; Brazil"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Infectious Diseases and Immunity in Global Health Program&#44; The Research Institute of the McGill University Health Centre&#44; Montreal&#44; QC&#44; Canada"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Graduate Program in Health Sciences&#44; School of Medicine&#44; Pontif&#237;cia Universidade Cat&#243;lica do Paran&#225;&#44; Curitiba&#44; PR&#44; Brazil"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "School of Life Sciences&#44; Pontif&#237;cia Universidade Cat&#243;lica do Paran&#225;&#44; Curitiba&#44; PR&#44; Brazil"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "School of Medicine&#44; Pontif&#237;cia Universidade Cat&#243;lica do Paran&#225;&#44; Curitiba&#44; PR&#44; Brazil"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 3138
            "Ancho" => 3341
            "Tamanyo" => 1107930
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Experimental design to test the mosaicism hypothesis in segmental vitiligo&#46; &#40;A&#41; Depiction of a segmental vitiligo patient&#46; Hypochromic areas highlighted with a full red circle would be evaluated for the presence of mosaic melanocytes&#46; A contralateral skin sample marked with a dotted circle would be used as an internal control&#46; &#40;B&#41; Skin composition for contralateral and hypochromic skin&#46; The hypochromic skin includes residual mosaic melanocytes&#46; &#40;C&#41; Subepidermal suction blister technique of normal and affected skin&#46; The trypsinization of the blister&#8217;s roof allows the detachment of keratinocytes and melanocytes that can be together with immune infiltrated cells used in the single-cell experiments&#46; &#40;D&#41; Single-cell barcoding&#46; The pool containing cell suspension for normal and affected skin would be loaded to the single-cell channel&#46; Individual cells would be incorporated into oil droplets and marked with unique barcoded beads&#44; which would allow the application of different sets of single-cell approaches including scWGS&#44; scRNA&#44; and scATAC&#46; &#40;E&#41; Cell clustering using omics data&#46; Clustering analysis would group cells sharing similar states and identify mosaic melanocytes as well as other cell types included in the blister extract&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">According to an international consensus&#44; vitiligo is classified into three main groups&#58; Segmental &#40;SV&#41;&#44; Non-Segmental &#40;NSV&#41;&#44; and mixed vitiligo &#40;coexistence of SV and NSV&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The consensus describes SV as a depigmentation spreading within a segment&#44; uni-&#44; bi-&#44; or pluri-segmental&#44; however&#44; this distribution can occasionally be bilateral&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> The segmental distribution pattern is not the only difference between SV and NSV &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The median age of SV onset is 16 years&#44; on average 8 to 10 years earlier than the median age of NSV onset&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a> Additionally&#44; depigmentation in SV typically has a rapid progression with a limited-time course between 6 to 24 months&#44; rarely extending after this period&#44; while NSV is chronic with an uncertain lifelong time course&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;6</span></a> In contrast to NSV&#44; SV presents early involvement of hair follicles melanocytes&#44; with up to 50&#37; of SV patients exhibiting poliosis in the affected area&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The prevalence of concomitant autoimmune disorders &#40;e&#46;g&#46;&#44; thyroiditis&#41; is lower in SV&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;7</span></a> SV and NSV also differ regarding response to treatment&#58; in general&#44; SV patients have a poor response to phototherapy compared to NSV&#44; possibly due to earlier depletion of follicular reservoir in the former&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> Conversely&#44; SV patients have an excellent and long-term response to surgical interventions such as melanocyte-keratinocyte transplant&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> The long-term success of transplant therapy in SV suggests a confined defect of melanocyte&#8211;keratinocyte metabolism&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Reports suggest differences in the biological mechanisms underlying the pathogenesis of SV as compared to NSV&#46; For example&#44; serum levels of TWEAK &#40;Tumor Necrosis Factor-like Weak inducer of Apoptosis&#41; were significantly higher in SV compared to NSV patients&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Moreover&#44; TWEAK was shown as a biomarker with 100&#37; sensitivity and 80&#46;1&#37; specificity in differentiating SV from NSV&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> In contrast to NSV&#44; systemic oxidative stress has a weak and limited contribution to SV pathogenesis&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> In SV&#44; a significant increase of stress-induced markers &#40;e&#46;g&#46;&#44; mitochondrial&#44; HSP70 and CXCL16&#41; was observed only in perilesional skin suggesting a localized pathogenic mechanism promoting depigmentation&#46; Immunophenotypic analysis of circulating immune cells of SV patients identified unaltered regulatory T-cells &#40;Tregs&#41; compared to healthy controls while NSV patients had decreased levels of Tregs&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Collectively&#44; multiple pieces of evidence indicate unaltered systemic immunity in SV patients and point to a localized cytotoxic reaction targeting epidermal melanocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Taken together&#44; these differences and the remarkable similarity of SV distribution pattern to mosaic melanocyte diseases &#40;as segmental lentiginose and verrucous epidermal nevus&#41; led us to hypothesize the involvement of somatic mosaicism in SV pathogenesis&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">How to test the hypothesis</span><p id="par0015" class="elsevierStylePara elsevierViewall">Mosaicism designates individuals encompassing at least two cell populations derived from a single zygote but with distinct genotype or epigenetic profiles&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> The phenotypic presentation of a disease caused by genetic mosaicism is conditional to the type of variation and phase of development that a somatic mutation that occurred&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Variants leading to genetic mosaicism range from chromosomal duplications&#44; segment translocations&#44; copy number variation &#40;CNV&#41;&#44; single-nucleotide variants &#40;SNV&#41;&#44; or epigenetic changes such as transcriptomic alterations caused by retrotransposition insertions&#46; The embryonic phase and cell differentiation status where a <span class="elsevierStyleItalic">de novo</span> mutation or retrotransposition occurred delineates the extent of tissues&#47;cells involved in the mosaicism&#46; The hypothesis to be tested suggest that genetic mosaicism in SV occurred at some point during skin&#47;melanocyte differentiation&#46; Different approaches can be applied to test the mosaicism hypothesis in SV&#44; each aiming to detect a distinct type of mosaicism&#46; Here we proposed examples by adapting designs applied to study the host response to infections&#44; detect somatic mutations in cancers and evaluate embryonic development&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;23</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Paired contrast of perilesional skin and contralateral healthy skin in SV</span><p id="par0020" class="elsevierStylePara elsevierViewall">The detection of mosaicism in human diseases can be challenging as the number of mosaic cells within the targeted tissue might be small&#46; In addition&#44; mosaic melanocytes would likely be absent inside existing SV lesions as a loss of melanocytes is the cause of vitiligo&#46; Therefore&#44; high-resolution methods at the single-cell level may be required to detect underrepresented cell populations&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> To detect potential mosaic cells&#44; evaluating tissue obtained from hypochromic skin regions from individuals at the earliest stage of SV would be required &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; An advantage of studying the mosaicism hypothesis in SV is the possibility to use internal controls since SV is usually constrained to a unilateral segment&#58; if the <span class="elsevierStyleItalic">de novo</span> mutation occurred during skin differentiation in one segment&#44; a contralateral healthy skin could be used to establish the melanocyte&#8217;s &#8220;normal&#8221; profile &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; This strategy would allow controlling for confounding effects caused by interindividual variability when combining multiple SV cases&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Target tissue preparation</span><p id="par0025" class="elsevierStylePara elsevierViewall">Melanocytes account for &#8764;2&#46;8&#37; of the cell population in the epidermis and approximately 1200 melanocytes exist per mm<span class="elsevierStyleSup">2</span> of the skin independently of an individual ethnicity &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> To capture a representative number of viable mosaic melanocytes for the single-cell analysis&#44; hypochromic areas of early-onset active SV would need to be determined using Wood&#8217;s lamp&#46; Keratinocyte-melanocyte sampling of these areas could be performed with a suction blister epidermal grafting technique with subsequent trypsinization of the blister&#8217;s roof to detach the cells into a suspension &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> An advantage of collecting epidermis by using the suction blister is the widening of the sampled area&#44; which increases the likelihood of capturing remaining viable mosaic melanocytes while being nearly a scarless technique&#44; which facilitates patient inclusion&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> To evaluate follicular melanoblasts not captured by the blister method&#44; a punch technique could also be used&#46; A punch biopsy is more invasive than blistering and the overall proportion of melanoblasts captured would be small&#46; However&#44; methodological refinements of single cell analysis could allow in a near future the study of smaller cell populations&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Identifying mosaic cells in segmental vitiligo via genetic and epigenetic variations</span><p id="par0030" class="elsevierStylePara elsevierViewall">To evaluate the presence of mosaic melanocytes&#44; fluorescence-activated cell sorting selection could be used to separate the melanocyte fraction of blister extracts or melanoblasts from punch biopsies&#46; Next&#44; whole genome sequencing &#40;WGS&#41; would be performed using DNA extracted from melanocytes from hypochromic and contralateral skin from the same individuals&#46; Variants detected in contralateral tissues would be used to exclude germline variants&#46; Algorithms designed to detect tumor cells&#44; such as MuTect2&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> or specific for mosaic cells&#44; such as MosaicForecast<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> and DeepMosaic&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> could be used to detect somatic mutations&#46; The limitation of the bulk approach is the inability to separate mosaic cells from regular melanocytes and evaluate their interaction with other cells&#46; Addressing this limitation would require single-cell &#40;sc&#41; sequencing technologies evaluating either the transcriptomic&#44; epigenetic&#44; or DNA sequence profile of individual cells &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> scWGS allows the evaluation of structural variation&#44; CNVs&#44; and SNVs in individual cells&#46; A high throughput scWGS method developed to detect subclonal mutations in cancer could be used to test the hypothesis of melanocyte mosaicism&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> In SV&#44; mosaic cells would share a state &#40;i&#46;e&#46;&#44; specific genetic variants&#41; that could be used to merge cells in clusters and define the proportion and the type of genetic variants present in mosaic cells &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>E&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> Epigenetic mosaicism in SV could be tested by using a multi-omics approach with transcriptomic &#40;scRNA&#41; and chromatin accessibility &#40;scATAC&#41; measures&#46; Multi-omics approaches are currently being used to study a diverse set of diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> Analyses of scRNA and scATAC could be used to identify mosaic cells via transcriptomic and epigenomic similarities with tools such as Seurat&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Monocle&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> and Cicero&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> A similar scRNA approach applied to study human embryos was able to successfully detect mosaicism&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> An advantage of the single cell compared to bulk approaches is the ability to study the relationship between cells present in the blister extract or punch biopsies&#46; In fact&#44; scRNA study of blistering extracts has shown the recovery of melanocytes from NSV lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Applying a single-cell approach to study SV could test the mosaicism hypothesis while assessing the local immune profile as shown for NSV&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Financial support</span><p id="par0035" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Authors&#8217; contributions</span><p id="par0040" class="elsevierStylePara elsevierViewall">Gerson Dellatorre&#58; Study concept&#44; writing and approval of the final manuscript&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Vinicius Medeiros Fava&#58; Study concept&#44; writing and approval of the final manuscript&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Marcelo T&#225;vora Mira&#58; Writing and approval of the final manuscript&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Caio Cesar Silva de Castro&#58; Study concept&#44; writing and approval of the final manuscript&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:8 [
        0 => array:3 [
          "identificador" => "xres1851029"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1609543"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        3 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "How to test the hypothesis"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Paired contrast of perilesional skin and contralateral healthy skin in SV"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Target tissue preparation"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Identifying mosaic cells in segmental vitiligo via genetic and epigenetic variations"
            ]
          ]
        ]
        4 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Financial support"
        ]
        5 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Authors&#8217; contributions"
        ]
        6 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Conflicts of interest"
        ]
        7 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2022-03-16"
    "fechaAceptado" => "2022-05-26"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1609543"
          "palabras" => array:3 [
            0 => "Genetics"
            1 => "Mosaicism"
            2 => "Vitiligo"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Vitiligo is an autoimmune disease of the skin that results in localized or disseminated white macules&#46; One common feature of several existing classification protocols is the distribution of the disease into two main subtypes&#44; non-segmental vitiligo &#40;NSV&#41; and segmental vitiligo &#40;SV&#41;&#46; SV is characterized by depigmentation spreading within one or more skin segments while NSV is widespread&#46; Several clinical-epidemiological observations suggest that SV has distinct autoimmune pathophysiology compared to NSV&#46; Furthermore&#44; the clinical distribution pattern of SV lesions closely resembles other melanocyte mosaicism diseases&#46; These observations led us to hypothesize that SV is caused by a localized autoimmune reaction targeting epidermal mosaicism melanocytes&#46; Here&#44; we proposed examples of experimental approaches to assess mosaicism in SV patients&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Pontif&#237;cia Universidade Cat&#243;lica do Paran&#225;&#44; Curitiba&#44; PR&#44; Brazil&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 3138
            "Ancho" => 3341
            "Tamanyo" => 1107930
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Experimental design to test the mosaicism hypothesis in segmental vitiligo&#46; &#40;A&#41; Depiction of a segmental vitiligo patient&#46; Hypochromic areas highlighted with a full red circle would be evaluated for the presence of mosaic melanocytes&#46; A contralateral skin sample marked with a dotted circle would be used as an internal control&#46; &#40;B&#41; Skin composition for contralateral and hypochromic skin&#46; The hypochromic skin includes residual mosaic melanocytes&#46; &#40;C&#41; Subepidermal suction blister technique of normal and affected skin&#46; The trypsinization of the blister&#8217;s roof allows the detachment of keratinocytes and melanocytes that can be together with immune infiltrated cells used in the single-cell experiments&#46; &#40;D&#41; Single-cell barcoding&#46; The pool containing cell suspension for normal and affected skin would be loaded to the single-cell channel&#46; Individual cells would be incorporated into oil droplets and marked with unique barcoded beads&#44; which would allow the application of different sets of single-cell approaches including scWGS&#44; scRNA&#44; and scATAC&#46; &#40;E&#41; Cell clustering using omics data&#46; Clustering analysis would group cells sharing similar states and identify mosaic melanocytes as well as other cell types included in the blister extract&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Segmental&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-segmental&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Median age of onset&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Earlier onset&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Later onset&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Association with autoimmune diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Less frequent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frequent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Role of early involvement of oxidative Stress&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unknown&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Present&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical Manifestation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Segmental&#44; unilateral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Varied&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Course&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Short and limited&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chronic and unstable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serum TWEAK levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tregs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unaffected&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diminished&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanocyte depletion at the follicle &#40;polyosis&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frequent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Less frequent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Response to clinical therapies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Poor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mod &#47; Good&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Long-term response to melanocyte-keratinocyte transplant procedure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Better&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Worse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Characteristics of segmental and non-segmental vitiligo&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:37 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Revised classification&#47;nomenclature of vitiligo and related issues&#58; the Vitiligo Global Issues Consensus Conference"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Ezzedine"
                            1 => "H&#46;W&#46; Lim"
                            2 => "T&#46; Suzuki"
                            3 => "I&#46; Katayama"
                            4 => "I&#46; Hamzavi"
                            5 => "C&#46;C&#46;E&#46; Lan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jpy.13323"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pigment Cell &#38; Melanoma Research"
                        "fecha" => "2012"
                        "volumen" => "25"
                        "paginaInicial" => "E1"
                        "paginaFinal" => "13"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36798977"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association between bilateral segmental vitiligo and lichen striatus&#58; an expression of mosaicism&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "L&#46;D&#46; Correia"
                            1 => "C&#46;C&#46;S&#46; Castro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Dermatol"
                        "fecha" => "2018"
                        "volumen" => "57"
                        "paginaInicial" => "992"
                        "paginaFinal" => "993"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A pattern of association between clinical form of vitiligo and disease-related variables in a Brazilian population"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46;C&#46;S&#46; Castro"
                            1 => "L&#46;M&#46; Nascimento"
                            2 => "M&#46; Olandoski"
                            3 => "M&#46;T&#46; Mira"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jdermsci.2011.09.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Dermatol Sci"
                        "fecha" => "2012"
                        "volumen" => "65"
                        "paginaInicial" => "63"
                        "paginaFinal" => "67"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22030153"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Jin"
                            1 => "G&#46;H&#46;L&#46; Roberts"
                            2 => "T&#46;M&#46; Ferrara"
                            3 => "S&#46; Ben"
                            4 => "N&#46; van Geel"
                            5 => "A&#46; Wolkerstorfer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41467-019-08337-4"
                      "Revista" => array:5 [
                        "tituloSerie" => "Nat Commun"
                        "fecha" => "2019"
                        "volumen" => "10"
                        "paginaInicial" => "391"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30674883"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Segmental vitiligo&#58; clinical findings in 208 patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46;K&#46; Hann"
                            1 => "H&#46;J&#46; Lee"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0190-9622(96)90718-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "1996"
                        "volumen" => "35"
                        "paginaInicial" => "671"
                        "paginaFinal" => "674"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8912558"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitiligo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "K&#46; Ezzedine"
                            1 => "V&#46; Eleftheriadou"
                            2 => "M&#46; Whitton"
                            3 => "N&#46; van Geel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(14)60763-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2015"
                        "volumen" => "386"
                        "paginaInicial" => "74"
                        "paginaFinal" => "84"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25596811"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comorbid autoimmune diseases in patients with vitiligo&#58; A cross-sectional study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46; Gill"
                            1 => "A&#46; Zarbo"
                            2 => "P&#46; Isedeh"
                            3 => "G&#46; Jacobsen"
                            4 => "H&#46;W&#46; Lim"
                            5 => "I&#46; Hamzavi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaad.2015.08.063"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "2016"
                        "volumen" => "74"
                        "paginaInicial" => "295"
                        "paginaFinal" => "302"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26518171"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation of the effects of NB-UVB in both segmental and non-segmental vitiligo affecting different body sites"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "T&#46;S&#46; Anbar"
                            1 => "W&#46; Westerhof"
                            2 => "A&#46;T&#46; Abdel-Rahman"
                            3 => "M&#46;A&#46; El-Khayyat"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Photodermatol Photoimmunol Photomed"
                        "fecha" => "2006"
                        "volumen" => "22"
                        "paginaInicial" => "157"
                        "paginaFinal" => "163"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Excimer light photototherapy of segmental and non-segmental vitiligo&#58; experience in Taiwan"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Y&#46;P&#46; Cheng"
                            1 => "H&#46;Y&#46; Chiu"
                            2 => "S&#46;H&#46; Jee"
                            3 => "T&#46;F&#46; Tsai"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1600-0781.2011.00628.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Photodermatol Photoimmunol Photomed"
                        "fecha" => "2012"
                        "volumen" => "28"
                        "paginaInicial" => "6"
                        "paginaFinal" => "11"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22211997"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term follow-up of patients undergoing autologous noncultured melanocyte-keratinocyte transplantation for vitiligo and other leukodermas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Silpa-Archa"
                            1 => "J&#46;L&#46; Griffth"
                            2 => "R&#46;H&#46; Huggins"
                            3 => "M&#46;D&#46; Henderson"
                            4 => "H&#46;A&#46; Kerr"
                            5 => "G&#46; Jacobsen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaad.2017.01.056"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "2017"
                        "volumen" => "77"
                        "paginaInicial" => "318"
                        "paginaFinal" => "327"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28502377"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Six-year follow-up of vitiligo patients successfully treated with autologous non-cultured melanocyte-keratinocyte transplantation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Altalhab"
                            1 => "M&#46;I&#46; AlJasser"
                            2 => "S&#46;V&#46; Mulekar"
                            3 => "A&#46;A&#46; Issa"
                            4 => "S&#46; Mulekar"
                            5 => "J&#46; Diaz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jdv.15411"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Eur Acad Dermatol Venereol&#46;"
                        "fecha" => "2019"
                        "volumen" => "33"
                        "paginaInicial" => "1172"
                        "paginaFinal" => "1176"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30793805"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serum TWEAK&#58; A cutoff between segmental and nonsegmental vitiligo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;E&#46;A&#46;I&#46; El-Taweel"
                            1 => "A&#46;M&#46;N&#46; Abdelrahman"
                            2 => "S&#46; Sabry"
                            3 => "R&#46;M&#46; Salem"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jocd.13644"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cosmet Dermatol"
                        "fecha" => "2021"
                        "volumen" => "20"
                        "paginaInicial" => "1017"
                        "paginaFinal" => "1021"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32808442"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "RIP1-Mediated Necroptosis Facilitates Oxidative StressInduced Melanocyte Death&#44; Offering Insight into Vitiligo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Li"
                            1 => "X&#46; Yi"
                            2 => "T&#46; Zhuang"
                            3 => "S&#46; Zhang"
                            4 => "S&#46; Li"
                            5 => "Y&#46; Yang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jid.2020.06.042"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Invest Dermatol"
                        "fecha" => "2021"
                        "volumen" => "141"
                        "paginaInicial" => "2921"
                        "paginaFinal" => "2931"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34102211"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Basic evidence for epidermal H2O2&#47;ONOO&#40;-&#41; &#8210; mediated oxidation&#47;nitration in segmental vitiligo is supported by repigmentation of skin and eyelashes after reduction of epidermal H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span> with topical NB-UVB-activated pseudocatalase PC-KUS"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "K&#46;U&#46; Schallreuter"
                            1 => "M&#46;A&#46;E&#46;L&#46; Salem"
                            2 => "S&#46; Holtz"
                            3 => "A&#46; Panske"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1096/fj.12-226779"
                      "Revista" => array:6 [
                        "tituloSerie" => "FASEB J"
                        "fecha" => "2013"
                        "volumen" => "27"
                        "paginaInicial" => "3113"
                        "paginaFinal" => "3122"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23629861"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunophenotypic analysis reveals differences in circulating immune cells in peripheral blood of segmental and non-segmental vitiligo patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Willemsen"
                            1 => "N&#46;F&#46; Post"
                            2 => "N&#46;O&#46;P&#46; van Uden"
                            3 => "V&#46;S&#46; Narayan"
                            4 => "S&#46; Chielie"
                            5 => "E&#46;H&#46; Kemp"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "J Invest Dermatol"
                        "fecha" => "2022"
                        "volumen" => "142"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Segmental vitiligo as the possible expression of cutaneous somatic mosaicism&#58; implications for common non-segmental vitiligo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Ta&#239;eb"
                            1 => "F&#46; Morice-Picard"
                            2 => "T&#46; Jouary"
                            3 => "K&#46; Ezzedine"
                            4 => "M&#46; Cario-Andr&#233;"
                            5 => "Y&#46; Gauthier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Pigment Cell &#38; Melanoma Research"
                        "fecha" => "2008"
                        "volumen" => "21"
                        "paginaInicial" => "646"
                        "paginaFinal" => "652"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The distribution pattern of segmental vitiligo&#58; clues for somatic mosaicism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; van Geel"
                            1 => "R&#46; Speeckaert"
                            2 => "E&#46; Melsens"
                            3 => "S&#46;P&#46; Toelle"
                            4 => "M&#46; Speeckaert"
                            5 => "S&#46; De Schepper"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/bjd.12013"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Dermatol"
                        "fecha" => "2013"
                        "volumen" => "168"
                        "paginaInicial" => "56"
                        "paginaFinal" => "64"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22913564"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A six-attribute classification of genetic mosaicism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46; Martinez-Glez"
                            1 => "J&#46; Tenorio"
                            2 => "J&#46; Nevado"
                            3 => "G&#46; Gordo"
                            4 => "L&#46; Rodr&#237;guez-Laguna"
                            5 => "M&#46; Feito"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41436-020-0877-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genet Med"
                        "fecha" => "2020"
                        "volumen" => "22"
                        "paginaInicial" => "1743"
                        "paginaFinal" => "1757"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32661356"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A genomic view of mosaicism and human disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "L&#46;G&#46; Biesecker"
                            1 => "N&#46;B&#46; Spinner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrg3424"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Genet"
                        "fecha" => "2013"
                        "volumen" => "14"
                        "paginaInicial" => "307"
                        "paginaFinal" => "320"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23594909"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Single-cell analysis of human embryos reveals diverse patterns of aneuploidy and mosaicism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;R&#46; Starostik"
                            1 => "O&#46;A&#46; Sosina"
                            2 => "R&#46;C&#46; McCoy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1101/gr.262774.120"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genome Res"
                        "fecha" => "2020"
                        "volumen" => "30"
                        "paginaInicial" => "814"
                        "paginaFinal" => "825"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32641298"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification of somatic mutations in single cell DNA-seq using a spatial model of allelic imbalance"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "L&#46;J&#46; Luquette"
                            1 => "C&#46;L&#46; Bohrson"
                            2 => "M&#46;A&#46; Sherman"
                            3 => "P&#46;J&#46; Park"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Nat Commum"
                        "fecha" => "2019"
                        "volumen" => "10"
                        "paginaInicial" => "3908"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Laks"
                            1 => "A&#46; McPherson"
                            2 => "H&#46; Zahn"
                            3 => "D&#46; Lai"
                            4 => "A&#46; Steif"
                            5 => "J&#46; Brimhall"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2019"
                        "volumen" => "179"
                        "itemHostRev" => array:3 [
                          "pii" => "S0002937815006699"
                          "estado" => "S300"
                          "issn" => "00029378"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A system biology approach identifies candidate drugs to reduce mortality in severely ill patients with COVID-19"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46;M&#46; Fava"
                            1 => "M&#46; Bourgey"
                            2 => "P&#46;M&#46; Nawarathna"
                            3 => "M&#46; Orlova"
                            4 => "P&#46; Cassart"
                            5 => "D&#46;C&#46; Vinh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Sci Adv&#46;"
                        "fecha" => "2022"
                        "volumen" => "8"
                        "paginaInicial" => "eabm2510"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in Treg function"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;J&#46; Gellatly"
                            1 => "J&#46;P&#46; Strassner"
                            2 => "K&#46; Essien"
                            3 => "M&#46;A&#46; Refat"
                            4 => "R&#46;L&#46; Murphy"
                            5 => "A&#46; Coffin-Schmitt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Sci Transl Med"
                        "fecha" => "2021"
                        "volumen" => "13"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alveolar macrophages from persons living with HIV show impaired epigenetic response to Mycobacterium tuberculosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46; Correa-Macedo"
                            1 => "V&#46;M&#46; Fava"
                            2 => "M&#46; Orlova"
                            3 => "P&#46; Cassart"
                            4 => "R&#46; Olivenstein"
                            5 => "J&#46; Sanz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2021"
                        "volumen" => "131"
                        "paginaInicial" => "e148013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Skin melanocytes&#58; biology and development"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Cichorek"
                            1 => "M&#46; Wachulska"
                            2 => "A&#46; Stasiewicz"
                            3 => "A&#46; Tyminska"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.5114/pdia.2013.33376"
                      "Revista" => array:6 [
                        "tituloSerie" => "Postepy Dermatol Alergol"
                        "fecha" => "2013"
                        "volumen" => "30"
                        "paginaInicial" => "30"
                        "paginaFinal" => "41"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24278043"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Noncultured epidermal suspension grafting using suction blisters as donor tissue for vitiligo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Tovar-Garza"
                            1 => "J&#46;A&#46; Hinojosa"
                            2 => "L&#46;S&#46; Hynan"
                            3 => "A&#46;G&#46; Pandya"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaad.2018.10.041"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "2019"
                        "volumen" => "80"
                        "paginaInicial" => "1152"
                        "paginaFinal" => "1154"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30393095"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Optimizing suction blister epidermal graft technique in the surgical treatment of vitiligo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G&#46; Dellatorre"
                            1 => "W&#46; Bertolini"
                            2 => "C&#46;C&#46;S&#46; Castro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1590/abd1806-4841.20176332"
                      "Revista" => array:6 [
                        "tituloSerie" => "An Bras Dermatol"
                        "fecha" => "2017"
                        "volumen" => "92"
                        "paginaInicial" => "888"
                        "paginaFinal" => "890"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29364459"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Calling Somatic SNVs and Indels with Mutect2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "D&#46; Benjamin"
                            1 => "T&#46; Sato"
                            2 => "K&#46; Cibulskis"
                            3 => "G&#46; Getz"
                            4 => "C&#46; Stewart"
                            5 => "L&#46; Linchtenstein"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "bioRxiv"
                        "fecha" => "2019"
                        "paginaInicial" => "1"
                        "paginaFinal" => "8"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Accurate detection of mosaic variants in sequencing data without matched controls"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Dou"
                            1 => "M&#46; Kwon"
                            2 => "R&#46;E&#46; Rodin"
                            3 => "I&#46; Cort&#233;s-Ciriano"
                            4 => "R&#46; Doan"
                            5 => "L&#46;J&#46; Luquette"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41587-019-0368-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature biotechnology"
                        "fecha" => "2020"
                        "volumen" => "38"
                        "paginaInicial" => "314"
                        "paginaFinal" => "319"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31907404"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "DeepMosaic&#58; Control-independent mosaic single nucleotide variant detection using deep convolutional neural networks"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "X&#46; Yang"
                            1 => "X&#46; Xu"
                            2 => "M&#46;W&#46; Breuss"
                            3 => "D&#46; Antaki"
                            4 => "L&#46;L&#46; Ball"
                            5 => "C&#46; Chung"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "bioRxiv"
                        "fecha" => "2021"
                        "paginaInicial" => "1"
                        "paginaFinal" => "38"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Single-cell analysis enters the multiomics age"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;M&#46; Perkel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2021"
                        "volumen" => "595"
                        "paginaInicial" => "614"
                        "paginaFinal" => "616"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comprehensive Integration of Single-Cell Data"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Stuart"
                            1 => "A&#46; Butler"
                            2 => "P&#46; Hoffman"
                            3 => "C&#46; Hafemeister"
                            4 => "E&#46; Papalexi"
                            5 => "W&#46;M&#46; Mauck 3rd"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2019"
                        "volumen" => "177"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multi-omics approaches to disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Y&#46; Hasin"
                            1 => "M&#46; Seldin"
                            2 => "A&#46; Lusis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13059-017-1215-1"
                      "Revista" => array:5 [
                        "tituloSerie" => "Genome Biol"
                        "fecha" => "2017"
                        "volumen" => "18"
                        "paginaInicial" => "83"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28476144"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Integrated analysis of multimodal single-cell data"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Hao"
                            1 => "S&#46; Hao"
                            2 => "E&#46; Andersen-N"
                            3 => "W&#46;M&#46; Mauck 3rd"
                            4 => "S&#46; Zheng"
                            5 => "A&#46; Butler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2021.04.048"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2021"
                        "volumen" => "184"
                        "paginaInicial" => "3573"
                        "paginaFinal" => "3587"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34062119"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The single-cell transcriptional landscape of mammalian organogenesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Cao"
                            1 => "M&#46; Spielmann"
                            2 => "X&#46; Qiu"
                            3 => "X&#46; Huang"
                            4 => "D&#46;M&#46; Ibrahim"
                            5 => "A&#46;J&#46; Hill"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41586-019-0969-x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2019"
                        "volumen" => "566"
                        "paginaInicial" => "496"
                        "paginaFinal" => "502"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30787437"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46;A&#46; Pliner"
                            1 => "J&#46;S&#46; Packer"
                            2 => "J&#46;L&#46; McFaline-Figueroa"
                            3 => "D&#46;A&#46; Cusanovich"
                            4 => "R&#46;M&#46; Daza"
                            5 => "D&#46; Aghamirzaie"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Mol Cell"
                        "fecha" => "2018"
                        "volumen" => "71"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/03650596/0000009800000002/v1_202302171515/S0365059622002847/v1_202302171515/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "87261"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Special Article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/03650596/0000009800000002/v1_202302171515/S0365059622002847/v1_202302171515/en/main.pdf?idApp=UINPBA00008Z&text.app=https://clinics.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622002847?idApp=UINPBA00008Z"
]

Article information

ISSN: 03650596
Original language: English

DOI:10.1016/j.abd.2022.05.001

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	26	4	30
2024 October	156	73	229
2024 September	205	92	297
2024 August	193	118	311
2024 July	146	95	241
2024 June	136	84	220
2024 May	92	71	163
2024 April	128	98	226
2024 March	115	74	189
2024 February	110	77	187
2024 January	73	63	136
2023 December	75	55	130
2023 November	93	93	186
2023 October	87	82	169
2023 September	148	86	234
2023 August	107	30	137
2023 July	85	49	134
2023 June	69	45	114
2023 May	76	25	101
2023 April	107	44	151
2023 March	127	73	200
2023 February	177	53	230
2023 January	42	51	93
2022 December	49	34	83

Show all

Indexed in:

Follow us:

Subscribe:

Statistics

Indexed in:

Follow us:

Subscribe:

Statistics

Subscribe to our newsletter