Stem cell repopulation efficiency but not pool size is governed by p27kip1
Tao Cheng, Neil Rodrigues, David Dombkowski, Sebastian Stier
& David T. Scadden
Massachusetts General Hospital AIDS Research Center and MGH Cancer Center, Harvard Medical School, 149 13th Street, Room 5212 Boston,
Massachusetts 02129.
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.
