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Updated: May 21, 2026
09:16
Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis
Published on: December 14, 2015
Diverse epigenetic strategies interact to control epidermal differentiation
Klaas W Mulder1, Xin Wang, Carles Escriu
1Epithelial Cell Biology Group, Cancer Research UK Cambridge Research Institute, Robinson Way, Cambridge CB2 0RE, UK. klaas.mulder@cancer.org.uk
Nature Cell Biology
|June 26, 2012
Summary
Functional gene networks, not single genes, control stem cell self-renewal and differentiation. This study identifies key epigenetic factors and their interactions regulating human epidermal stem cell differentiation.
Area of Science:
- Epigenetics
- Stem Cell Biology
- Genomics
Background:
- Stem cell self-renewal and differentiation are governed by complex gene networks.
- Epigenetic factors play a crucial role in regulating these processes.
- Identifying these factors is key to understanding stem cell behavior.
Purpose of the Study:
- To identify epigenetic factors influencing human epidermal stem cell differentiation.
- To uncover functional interactions between chromatin modifiers.
- To elucidate the regulatory mechanisms of epidermal stem cell fate.
Main Methods:
- Performed siRNA-based genetic screens of 332 chromatin modifiers.
- Developed a Bayesian mixture model for predicting functional interactions.
- Conducted genome-wide localization and mRNA expression analysis.
- Utilized competitive epidermal reconstitution assays.
Main Results:
- Discovered a network of interactions involving EZH2, UHRF1, ING5, BPTF, and SMARCA5.
- Identified impacts on gene sets including integrin extracellular matrix receptors.
- Confirmed the role of these factors in controlling differentiation under physiological conditions.
Conclusions:
- Interplay between diverse epigenetic strategies regulates distinct gene expression programs.
- These epigenetic mechanisms protect epidermal stem cells from premature differentiation.
- Understanding these networks is vital for stem cell therapies.
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