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DNA methyltransferase-3-dependent nonrandom template segregation in differentiating embryonic stem cells
Christian Elabd1, Wendy Cousin, Robert Y Chen
1Department of Bioengineering, 2 Stem Cell Center, and 3 QB3 Institute, University of California, Berkeley, Berkeley, CA 94720.
The Journal of Cell Biology
|October 16, 2013
Summary
Stem cells divide asymmetrically, with one daughter cell renewing and the other differentiating. This study reveals nonrandom template segregation (NRTS) of chromatids in differentiating stem cells, regulated by DNA methylation and Dnmt3.
Area of Science:
- Stem cell biology
- Epigenetics
- Cellular differentiation
Background:
- Asymmetric cell fate is crucial for stem cell self-renewal and differentiation.
- Nonrandom template segregation (NRTS) of chromosomes has been observed in various organisms.
- The mechanism of asymmetric chromatid inheritance in differentiating stem cells was previously unknown.
Purpose of the Study:
- To demonstrate NRTS in differentiating embryonic stem cells (ESCs).
- To elucidate the molecular mechanism regulating NRTS in ESCs.
Main Methods:
- Investigated chromatid segregation in differentiating human and mouse ESCs.
- Assessed the role of DNA methylation and Dnmt3 in NRTS.
Main Results:
- Unambiguously demonstrated NRTS in asymmetrically dividing, differentiating human and mouse ESCs.
- Showed that NRTS is dependent on DNA methylation and Dnmt3.
- Provided evidence that "old" DNA strands retain epigenetic memory, while "new" strands facilitate adaptation.
Conclusions:
- NRTS is a key mechanism in differentiating ESCs.
- DNA methylation and Dnmt3 regulate NRTS.
- This process ensures faithful inheritance of cell fate memory and adaptation to new fates.
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