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

Nat Med. 2000 Nov;6(11):1235-40. doi: 10.1038/81335.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Cell Cycle
  • Cell Cycle Proteins*
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Crosses, Genetic
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Female
  • Flow Cytometry
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / physiology*
  • Heterozygote
  • Homozygote
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Microtubule-Associated Proteins / deficiency
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / physiology*
  • Tumor Suppressor Proteins*

Substances

  • Cdkn1b protein, mouse
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases