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Nat Med. 2000 Nov;6(11):1235-40.

Stem cell repopulation efficiency but not pool size is governed by p27(kip1).

Author information

1
Massachusetts General Hospital AIDS Research Center, Harvard Medical School, 149 13th Street, Room 5212 Boston, Massachusetts 02129, USA. cheng-tao@mgh.harvard.edu

Abstract

Sustained blood cell production requires preservation of a quiescent, multipotential stem cell pool that intermittently gives rise to progenitors with robust proliferative potential. The ability of cells to shift from a highly constrained to a vigorously active proliferative state is critical for maintaining stem cells while providing the responsiveness necessary for host defense. The cyclin-dependent kinase inhibitor (CDKI), p21(cip1/waf1) (p21) dominates stem cell kinetics. Here we report that another CDKI, p27(kip1) (p27), does not affect stem cell number, cell cycling, or self-renewal, but markedly alters progenitor proliferation and pool size. Therefore, distinct CDKIs govern the highly divergent stem and progenitor cell populations. When competitively transplanted, p27-deficient stem cells generate progenitors that eventually dominate blood cell production. Modulating p27 expression in a small number of stem cells may translate into effects on the majority of mature cells, thereby providing a strategy for potentiating the impact of transduced cells in stem cell gene therapy.

PMID:
11062534
DOI:
10.1038/81335
[Indexed for MEDLINE]

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