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The polycomb protein Ezh2 impacts on induced pluripotent stem cell generation
Xiaolei Ding1, Xiaoying Wang, Stephanie Sontag
11 Department of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School , Aachen, Germany .
Stem Cells and Development
|December 12, 2013
Summary
Enhancer of Zeste homolog 2 (Ezh2) is crucial for generating induced pluripotent stem (iPS) cells by repressing the Ink4a/Arf locus. However, Ezh2 is not essential for maintaining pluripotency in established iPS cells.
Area of Science:
- Epigenetics and Gene Regulation
- Stem Cell Biology
- Cellular Reprogramming
Background:
- Polycomb group (PcG) proteins regulate chromatin structure, cell identity, and development.
- Ezh2, a core subunit of Polycomb repressive complex 2 (PRC2), is implicated in these processes.
Purpose of the Study:
- To investigate the role of Ezh2 in the generation of induced pluripotent stem (iPS) cells.
- To elucidate the mechanisms by which Ezh2 influences reprogramming.
Main Methods:
- Somatic cell reprogramming into iPS cells.
- shRNA-mediated knockdown of Ezh2 expression.
- Quantitative analysis of Ezh2 mRNA and protein levels.
- Assessment of Ink4a/Arf locus regulation.
Main Results:
- Ezh2 expression is upregulated during iPS cell generation and is abundant in iPS cells.
- Knockdown of Ezh2 significantly impairs iPS cell generation.
- Ezh2 represses the Ink4a/Arf locus, a key barrier to reprogramming.
- Ezh2 is not required for maintaining pluripotency in established iPS cells.
Conclusions:
- Ezh2 is essential for efficient induction of pluripotency.
- Ezh2 functions by silencing critical developmental roadblocks like the Ink4a/Arf locus during reprogramming.
- Ezh2's role is specific to the reprogramming process, not the maintenance of pluripotency.
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