Title | p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity. |
Publication Type | Journal Article |
Year of Publication | 2005 |
Authors | Kippin TE, Martens DJ, van der Kooy D |
Journal | Genes Dev |
Volume | 19 |
Issue | 6 |
Pagination | 756-67 |
Date Published | 2005 Mar 15 |
ISSN | 0890-9369 |
Keywords | Analysis of Variance, Animals, Apoptosis, Bromodeoxyuridine, Cell Count, Cell Cycle, Cell Cycle Proteins, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21, Flow Cytometry, Hematopoietic Stem Cells, Immunohistochemistry, Mice, Mice, Mutant Strains, Microscopy, Fluorescence, Prosencephalon |
Abstract | 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. |
DOI | 10.1101/gad.1272305 |
Alternate Journal | Genes Dev. |
PubMed ID | 15769947 |
PubMed Central ID | PMC1065728 |