| First Author | Marqués-Torrejón MÁ | Year | 2013 |
| Journal | Cell Stem Cell | Volume | 12 |
| Issue | 1 | Pages | 88-100 |
| PubMed ID | 23260487 | Mgi Jnum | J:345268 |
| Mgi Id | MGI:6837150 | Doi | 10.1016/j.stem.2012.12.001 |
| Citation | Marques-Torrejon MA, et al. (2013) Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression. Cell Stem Cell 12(1):88-100 |
| abstractText | In the adult brain, continual neurogenesis of olfactory neurons is sustained by the existence of neural stem cells (NSCs) in the subependymal niche. Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control and long-term self-renewal, but the molecular mechanisms underlying NSC maintenance by p21 remain unexplored. Here we identify a function of p21 in the direct regulation of the expression of pluripotency factor Sox2, a key regulator of the specification and maintenance of neural progenitors. We observe that p21 directly binds a Sox2 enhancer and negatively regulates Sox2 expression in NSCs. Augmented levels of Sox2 in p21 null cells induce replicative stress and a DNA damage response that leads to cell growth arrest mediated by increased levels of p19(Arf) and p53. Our results show a regulation of NSC expansion driven by a p21/Sox2/p53 axis. |
