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Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis
Published on: December 14, 2015
Polycomb subunits Ezh1 and Ezh2 regulate the Merkel cell differentiation program in skin stem cells.
Evan S Bardot1, Victor J Valdes, Jisheng Zhang
1Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
The EMBO Journal
|May 16, 2013
Summary
The Polycomb complex maintains epidermal progenitor cells by repressing Sox2. Removing Ezh1/Ezh2 increases Merkel cells, while Sox2 is essential for their development.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Epigenetics
Background:
- The Polycomb complex regulates cell identity in embryonic stem cells.
- Its role in tissue-specific stem cells, like those in skin, is less understood.
Purpose of the Study:
- To investigate the Polycomb complex's role in epidermal progenitor cell differentiation.
- To identify the genetic mechanisms governing Merkel cell development.
Main Methods:
- Genetic ablation of Ezh1 and Ezh2 in mouse skin.
- Analysis of epidermal progenitor cell fate determination.
- Investigating the role of transcription factors Sox2 and Atoh1.
Main Results:
- Removal of Ezh1/Ezh2 increased Merkel cell numbers by derepressing Sox2.
- Sox2 is critical for Merkel cell specification, activating Atoh1.
- Sox2 ablation counteracted the Ezh1/Ezh2-null phenotype.
Conclusions:
- The Polycomb complex maintains the epidermal progenitor state by repressing Sox2.
- A novel regulatory network involving Polycomb, Sox2, and Atoh1 governs skin stem cell differentiation.
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