SNAI2 Controls the Undifferentiated State of Human Epidermal Progenitor Cells

Authors

  • Devendra S. Mistry,

    1. Department of Dermatology, University of California, La Jolla, San Diego, California, USA
    2. Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, La Jolla, San Diego, California, USA
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  • Yifang Chen,

    1. Department of Dermatology, University of California, La Jolla, San Diego, California, USA
    2. Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, La Jolla, San Diego, California, USA
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  • Ying Wang,

    1. Department of Dermatology, University of California, La Jolla, San Diego, California, USA
    2. Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, La Jolla, San Diego, California, USA
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  • Kang Zhang,

    1. Department of Ophthalmology, University of California, La Jolla, San Diego, California, USA
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  • George L. Sen

    Corresponding author
    1. Department of Dermatology, University of California, La Jolla, San Diego, California, USA
    2. Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, La Jolla, San Diego, California, USA
    • Correspondence: George L. Sen, Ph.D., Department of Dermatology, Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, La Jolla, San Diego, California 92093-0869, USA. Telephone: 858-246-0268; e-mail: gsen@ucsd.edu

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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. Stem Cells 2014;32:3209–3218

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