Prolonged cell cycle transit is a defining and developmentally conserved hemopoietic stem cell property

JM Nygren, D Bryder, SEW Jacobsen - The Journal of immunology, 2006 - journals.aai.org
JM Nygren, D Bryder, SEW Jacobsen
The Journal of immunology, 2006journals.aai.org
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 …
Abstract
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 SG 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.
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