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Adult mouse hemopoietic stem cells (HSCs) are typically quiescent and enter and progress through the cell cycle rarely in steady-state bone marrow, but their rate of proliferation can be dramatically enhanced on demand. We have studied the cell cycle kinetics of HSCs in the developing fetal liver at a stage when they expand extensively. Despite that 100% of fetal liver HSCs divide within a 48-h period, their average cell cycle transit time (10.6 h) is twice that of their downstream progenitors, translating into a prolonged G(1) transit and a period of relative quiescence (G(0)). In agreement with their prolonged G(1) transit when compared with hemopoietic progenitors, competitive transplantation experiments demonstrate that fetal HSCs are highly enriched in G(1) but also functional in S-G(2)-M. This observation combined with experimental data demonstrating that adult HSCs forced to expand ex vivo also sustain a uniquely prolonged cell cycle and G(1) transit, demonstrate at least in part why purified HSCs at any state of development or condition are highly enriched in the G(0)-G(1) phases of the cell cycle. We propose that a uniquely prolonged cell cycle transit is a defining stem cell property, likely to be critical for their maintenance and self-renewal throughout development.

Original publication

DOI

10.4049/jimmunol.177.1.201

Type

Journal article

Journal

J Immunol

Publication Date

01/07/2006

Volume

177

Pages

201 - 208

Keywords

Animals, Cell Cycle, Cell Differentiation, Cell Division, Cell Proliferation, Cellular Senescence, Fetus, G1 Phase, G2 Phase, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Liver, Liver Transplantation, Mice, Mice, Congenic, Mice, Inbred C57BL, Multipotent Stem Cells, Resting Phase, Cell Cycle, S Phase, Time Factors