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An Efficient Method for Directed Hepatocyte-Like Cell Induction from Human Embryonic Stem Cells
Published on: May 6, 2021
Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells
Elena Ezhkova1, H Amalia Pasolli, Joel S Parker
1Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
Cell
|March 24, 2009
Summary
Polycomb repressor complexes (PRCs) regulate epidermal progenitor cell differentiation. Ezh2, a PRC component, maintains progenitor proliferation and controls differentiation timing by repressing specific genes.
Area of Science:
- Developmental biology
- Epigenetics
- Stem cell biology
Background:
- Polycomb repressor complexes (PRCs) are known regulators of embryonic stem cell differentiation.
- The role of PRCs in controlling multipotent progenitor differentiation in developing tissues is not well understood.
Purpose of the Study:
- To investigate the role of Ezh2, an essential PRC component, in epidermal progenitor cell differentiation.
- To elucidate the mechanisms by which Ezh2 controls progenitor proliferation and differentiation timing.
Main Methods:
- Analysis of Ezh2 expression in epidermal progenitors during embryonic and postnatal development.
- Investigating the effect of Ezh2 on the Ink4A-Ink4B locus and AP1 transcriptional activator recruitment.
- Studying the temporal and spatial control of epigenetic modifications in tissue-restricted stem cells.
Main Results:
- Ezh2 expression in epidermal progenitors decreases with differentiation and reduced proliferative activity.
- Ezh2 represses the Ink4A-Ink4B locus, controlling basal progenitor proliferative potential.
- Ezh2 prevents premature AP1 recruitment to differentiation genes, tempering the rate of epidermal differentiation.
Conclusions:
- PRCs, through Ezh2, exert temporal and spatial epigenetic control over tissue-restricted stem cells.
- PRCs maintain progenitor proliferative potential by globally repressing differentiation.
- PRCs selectively establish terminal differentiation programs in a stepwise manner.
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