title: SNAI2 controls the undifferentiated state of human epidermal progenitor cells.
abstract: The transcription factor, SNAI2, is an inducer of the epithelial to mesenchymal transition (EMT) which mediates cell migration during development and tumor invasion. SNAI2 can also promote the generation of mammary epithelial stem cells from differentiated luminal cells when overexpressed. How SNAI2 regulates these critical and diverse functions is unclear. Here, we show that the levels of SNAI2 expression are important for epidermal cell fate decisions. The expression of SNAI2 was found to be enriched in the basal layer of the interfollicular epidermis where progenitor cells reside and extinguished upon differentiation. Loss of SNAI2 resulted in premature differentiation whereas gain of SNAI2 expression inhibited differentiation. SNAI2 controls the differentiation status of epidermal progenitor cells by binding to and repressing the expression of differentiation genes with increased binding leading to further transcriptional silencing. Thus, the levels of SNAI2 binding to genomic targets determine the differentiation status of epithelial cells with increased levels triggering EMT and dedifferentiation, moderate (physiological) levels promoting epidermal progenitor function, and low levels leading to epidermal differentiation.
authors.affiliation: Department of Dermatology, University of California, La Jolla, San Diego, California, USA; Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, La Jolla, San Diego, California, USA.
authors.forename: Devendra S
authors.initials: DS
authors.lastname: Mistry
authors.forename: Yifang
authors.initials: Y
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.forename: George L
authors.initials: GL
authors.lastname: Sen
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D000071250:Snail Family Transcription Factors; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
keywords: ChIP-Seq; Differentiation; Epidermal differentiation; Epidermis; Epithelial to mesenchymal transition; Epithelium; GRHL3; KLF4; Metastasis; Progenitor cell; SLUG; SNAI2; SNAIL; Skin differentiation; Stem cell; Transcription factor
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