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.
References
52
Referenced
350
10.1084/jem.193.8.917
10.1111/j.1471-4159.2004.02472.x
10.1016/S0531-5565(00)00083-8
10.1126/science.287.5459.1804
10.1002/(SICI)1096-9861(19960101)364:1<6::AID-CNE2>3.0.CO;2-9
10.1523/JNEUROSCI.22-06-02255.2002
/ J. Neurosci. (2002)10.1523/JNEUROSCI.2751-04.2004
10.1242/dev.01215
10.1126/science.287.5457.1433
{'key': '2021111607251077000_19.6.756.10', 'first-page': '495', 'volume': '25', 'year': '1997', 'journal-title': 'Exp. Hematol.'}
/ Exp. Hematol. (1997)10.1016/S0304-3940(00)01580-9
10.1126/science.1065518
10.1038/345458a0
10.1016/0014-4827(65)90211-9
10.1054/bjoc.2000.1296
10.1101/gad.975202
10.1523/JNEUROSCI.0110-04.2004
10.1126/science.8178174
10.1016/0896-6273(93)90281-U
10.1523/JNEUROSCI.20-03-01085.2000
/ J. Neurosci. (2000)10.1046/j.1460-9568.2002.02181.x
10.1523/JNEUROSCI.4608-03.2004
10.1126/science.1056782
10.1016/0360-3016(94)00430-S
10.1038/nature02060
10.1523/JNEUROSCI.12-01-00249.1992
/ J. Neurosci. (1992)10.1016/j.conb.2004.01.008
10.1016/0896-6273(94)90046-9
10.1242/dev.125.12.2251
/ Development (1998)10.1038/nm0302-268
10.1046/j.1460-9568.2003.02727.x
- Musunuru K . and Hinds, P.W. 1997. Cell cycle regulators in cancer. Karger Landes Systems, Basel, NY.
{'key': '2021111607251077000_19.6.756.33', 'first-page': '2844', 'volume': '81', 'year': '1994', 'journal-title': 'Blood'}
/ Blood (1994)10.1097/00001622-200001000-00013
{'key': '2021111607251077000_19.6.756.35', 'first-page': '1273', 'volume': '151', 'year': '1997', 'journal-title': 'Am. J. Pathol.'}
/ Am. J. Pathol. (1997){'key': '2021111607251077000_19.6.756.36', 'first-page': '369', 'volume': '13', 'year': '2002', 'journal-title': 'Cell Dev. Biol.'}
/ Cell Dev. Biol. (2002)10.1084/jem.20031385
10.1006/dbio.1996.0090
10.1523/JNEUROSCI.22-05-01784.2002
/ J. Neurosci. (2002)10.1016/S0166-2236(03)00031-6
10.1016/j.ydbio.2004.10.017
10.1038/nature01119
10.1006/excr.1997.3824
10.1038/35036093
10.1126/science.1056780
10.1006/dbio.1998.9192
10.1126/science.287.5457.1439
10.1016/S0378-1119(00)00092-5
10.1016/S0531-5565(01)00165-6
10.1002/(SICI)1097-4695(199808)36:2<307::AID-NEU14>3.0.CO;2-A
10.1126/science.287.5457.1442
10.1146/annurev.cellbio.17.1.387
Dates
Type | When |
---|---|
Created | 20 years, 5 months ago (March 15, 2005, 10:38 a.m.) |
Deposited | 3 years, 9 months ago (Nov. 16, 2021, 5:26 a.m.) |
Indexed | 4 days, 5 hours ago (Sept. 3, 2025, 6:46 a.m.) |
Issued | 20 years, 5 months ago (March 15, 2005) |
Published | 20 years, 5 months ago (March 15, 2005) |
Published Online | 20 years, 5 months ago (March 15, 2005) |
Published Print | 20 years, 5 months ago (March 15, 2005) |
@article{Kippin_2005, title={p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity}, volume={19}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1272305}, DOI={10.1101/gad.1272305}, number={6}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Kippin, Tod E. and Martens, David J. and van der Kooy, Derek}, year={2005}, month=mar, pages={756–767} }