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Cohesin's role in pluripotency and reprogramming.
Preksha Gupta1, Thais Lavagnolli1, Hegias Mira-Bontenbal1
1a Lymphocyte Development Group, MRC Clinical Sciences Center, Faculty of Medicine, Imperial College London , London , UK.
Cell Cycle (Georgetown, Tex.)
|December 25, 2015
Summary
Cohesin is crucial for cell pluripotency and reprogramming. DNA damage, not cohesin loss, hinders pluripotency gene expression, suggesting cohesin’s role is tied to cell cycle functions.
Area of Science:
- Cell Biology
- Genetics
- Developmental Biology
Background:
- Cohesin is vital for embryonic stem (ES) cell self-renewal and induced pluripotent stem (iPS) cell reprogramming.
- Its role in pluripotency gene regulation may involve chromosomal interactions, but cohesin also maintains genome integrity.
- Depletion of cohesin in dividing cells triggers DNA damage responses, complicating the understanding of its precise function in pluripotency.
Purpose of the Study:
- To differentiate between cohesin's role in maintaining long-range chromosomal interactions versus its role in preventing DNA damage responses.
- To investigate the direct impact of DNA damage on pluripotency and reprogramming.
- To clarify the specific functions of cohesin in the context of cell cycle progression and pluripotency.
Main Methods:
- Analysis of cellular reprogramming in the absence of cell division.
- Acute depletion of cohesin in ES cells.
- Assessment of pluripotency gene expression following cohesin depletion.
- Deliberate induction of DNA damage in cells.
Main Results:
- Cohesin is not specifically required for reprogramming when cell division is inhibited.
- Most pluripotency genes remain expressed upon acute cohesin depletion in ES cells.
- Induced DNA damage directly impairs pluripotency and reprogramming, as does DNA damage from cohesin loss during proliferation.
Conclusions:
- The observed effects of cohesin depletion on pluripotency and reprogramming are likely mediated by DNA damage responses.
- Cohesin's essential functions in the cell cycle, rather than direct regulation of pluripotency genes, may explain its role in pluripotency and reprogramming.
- Preventing DNA damage is critical for maintaining pluripotency and successful reprogramming.
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