Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation

Anna V. Molofsky, Ricardo Pardal, Toshihide Iwashita, In-Kyung Park, Michael F. Clarke and Sean J. Morrison ()
Additional contact information
Anna V. Molofsky: University of Michigan
Ricardo Pardal: University of Michigan
Toshihide Iwashita: University of Michigan
Michael F. Clarke: University of Michigan
Sean J. Morrison: University of Michigan

Nature, 2003, vol. 425, issue 6961, 962-967

Abstract: Abstract Stem cells persist throughout life by self-renewing in numerous tissues including the central1 and peripheral2 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 defects3. 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 p16Ink4a is upregulated in neural stem cells, reducing the rate of proliferation. p16Ink4a 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 p16Ink4a 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.

Date: 2003
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature02060 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:425:y:2003:i:6961:d:10.1038_nature02060

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature02060

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().