First Author | Kippin TE | Year | 2005 |
Journal | Genes Dev | Volume | 19 |
Issue | 6 | Pages | 756-67 |
PubMed ID | 15769947 | Mgi Jnum | J:105510 |
Mgi Id | MGI:3615728 | Doi | 10.1101/gad.1272305 |
Citation | Kippin TE, et al. (2005) p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity. Genes Dev 19(6):756-67 |
abstractText | Adult stem cells in various tissues are relatively quiescent. The cell cycle inhibitor p21cip1/waf1 (p21) has been shown to be important for maintaining hematopoietic stem cell quiescence and self-renewal. We examined the role of p21 in the regulation of adult mammalian forebrain neural stem cells (NSCs). We found that p21-/- mice between post-natal age 60-240 d have more NSCs than wild-type (+/+) controls due to higher proliferation rates of p21-/- NSCs. Thereafter, NSCs in p21-/- mice decline and are reduced in number at 16 mo relative to p21+/+ mice. Similarly, both p21-/- and p21+/+ NSCs display self-renewal in vitro; however, p21-/- NSCs display limited in vitro self-renewal (surviving a few passages, then exhausting). Thus, p21 contributes to adult NSC relative quiescence, which we propose is necessary for the life-long maintenance of NSC self-renewal because NSCs may be limited to a finite number of divisions. |