Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation
dc.contributor.author | Molofsky, Anna V. | en_US |
dc.contributor.author | Pardal, Ricardo | en_US |
dc.contributor.author | Iwashita, T. | en_US |
dc.contributor.author | Park, In-Kyung | en_US |
dc.contributor.author | Clarke, Michael. F. | en_US |
dc.contributor.author | Morrison, Sean J. | en_US |
dc.date.accessioned | 2009-06-01T17:33:54Z | |
dc.date.available | 2009-06-01T17:33:54Z | |
dc.date.issued | 2003-10-30 | en_US |
dc.identifier.citation | Molofsky, AV; Pardal, R; Iwashita, T; Park, IK; Clarke, MF; Morrison, SJ. (2003) "Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation." Nature 425(6961): 962-967. <http://hdl.handle.net/2027.42/62726> | en_US |
dc.identifier.issn | 0028-0836 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/62726 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=14574365&dopt=citation | en_US |
dc.description.abstract | Stem cells persist throughout life by self-renewing in numerous tissues including the central(1) and peripheral(2) nervous systems. This raises the issue of whether there is a conserved mechanism to effect self-renewing divisions. Deficiency in the polycomb family transcriptional repressor Bmi-1 leads to progressive postnatal growth retardation and neurological defects(3). Here we show that Bmi-1 is required for the self-renewal of stem cells in the peripheral and central nervous systems but not for their survival or differentiation. The reduced self-renewal of Bmi-1-deficient neural stem cells leads to their postnatal depletion. In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16(Ink4a) is upregulated in neural stem cells, reducing the rate of proliferation. p16(Ink4a) deficiency partially reverses the self-renewal defect in Bmi-1(-/-) neural stem cells. This conserved requirement for Bmi-1 to promote self-renewal and to repress p16(Ink4a) expression suggests that a common mechanism regulates the self-renewal and postnatal persistence of diverse types of stem cell. Restricted neural progenitors from the gut and forebrain proliferate normally in the absence of Bmi-1. Thus, Bmi-1 dependence distinguishes stem cell self-renewal from restricted progenitor proliferation in these tissues. | en_US |
dc.format.extent | 402693 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/octet-stream | |
dc.format.mimetype | text/plain | |
dc.publisher | Nature Publishing Group | en_US |
dc.source | Nature | en_US |
dc.title | Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA | en_US |
dc.identifier.pmid | 14574365 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/62726/1/nature02060.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1038/nature02060 | en_US |
dc.identifier.source | Nature | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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