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, Sean J. Morrison

Research output: Contribution to journalArticle

1026 Citations (Scopus)

Abstract

Stem cells persist throughout life by self-renewing in numerous tissues including the central and peripheral 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. 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 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.

Original languageEnglish (US)
Pages (from-to)962-967
Number of pages6
JournalNature
Volume425
Issue number6961
DOIs
StatePublished - Oct 30 2003

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Neural Stem Cells
Peripheral Nervous System
Stem Cells
Central Nervous System
CDC2 Protein Kinase
p16 Genes
Prosencephalon
Growth
Cell Self Renewal

ASJC Scopus subject areas

  • General

Cite this

Molofsky, A. V., Pardal, R., Iwashita, T., Park, I. K., Clarke, M. F., & Morrison, S. J. (2003). Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature, 425(6961), 962-967. https://doi.org/10.1038/nature02060

Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. / Molofsky, Anna V.; Pardal, Ricardo; Iwashita, Toshihide; Park, In Kyung; Clarke, Michael F.; Morrison, Sean J.

In: Nature, Vol. 425, No. 6961, 30.10.2003, p. 962-967.

Research output: Contribution to journalArticle

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, vol. 425, no. 6961, pp. 962-967. https://doi.org/10.1038/nature02060
Molofsky, Anna V. ; Pardal, Ricardo ; Iwashita, Toshihide ; Park, In Kyung ; Clarke, Michael F. ; Morrison, Sean J. / Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. In: Nature. 2003 ; Vol. 425, No. 6961. pp. 962-967.
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