First Author | Cheng T | Year | 2000 |
Journal | Nat Med | Volume | 6 |
Issue | 11 | Pages | 1235-40 |
PubMed ID | 11062534 | Mgi Jnum | J:65495 |
Mgi Id | MGI:1926666 | Doi | 10.1038/81335 |
Citation | Cheng T, et al. (2000) Stem cell repopulation efficiency but not pool size is governed by p27kip1. Nat Med 6(11):1235-40 |
abstractText | 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. |