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

Cheng, Tao, Rodrigues, Neil ORCID: https://orcid.org/0000-0002-1925-7733, Dombkowski, David, Stier, Sebastian and Scadden, David T. 2000. Stem cell repopulation efficiency but not pool size is governed by p27 (kip1). Nature Medicine 6 , pp. 1235-1240. 10.1038/81335

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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), p21cip1/waf1 (p21) dominates stem cell kinetics. Here we report that another CDKI, p27kip1 (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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Subjects:	Q Science > QR Microbiology
Publisher:	Nature Publishing Group
ISSN:	1078-8956
Last Modified:	22 Jun 2023 10:01
URI:	https://orca.cardiff.ac.uk/id/eprint/65030

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