| First Author | Su J | Year | 2019 |
| Journal | Cell Rep | Volume | 28 |
| Issue | 6 | Pages | 1400-1409.e4 |
| PubMed ID | 31390555 | Mgi Jnum | J:300462 |
| Mgi Id | MGI:6489054 | Doi | 10.1016/j.celrep.2019.07.011 |
| Citation | Su J, et al. (2019) Genomic Integrity Safeguards Self-Renewal in Embryonic Stem Cells. Cell Rep 28(6):1400-1409.e4 |
| abstractText | A multitude of signals are coordinated to maintain self-renewal in embryonic stem cells (ESCs). To unravel the essential internal and external signals required for sustaining the ESC state, we expand upon a set of ESC pluripotency-associated phosphoregulators (PRs) identified previously by short hairpin RNA (shRNA) screening. In addition to the previously described Aurka, we identify 4 additional PRs (Bub1b, Chek1, Ppm1g, and Ppp2r1b) whose depletion compromises self-renewal and leads to consequent differentiation. Global gene expression profiling and computational analyses reveal that knockdown of the 5 PRs leads to DNA damage/genome instability, activating p53 and culminating in ESC differentiation. Similarly, depletion of genome integrity-associated genes involved in DNA replication and checkpoint, mRNA processing, and Charcot-Marie-Tooth disease lead to compromise of ESC self-renewal via an increase in p53 activity. Our studies demonstrate an essential link between genomic integrity and developmental cell fate regulation in ESCs. |
