In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells

SH Cheshier, SJ Morrison, X Liao… - Proceedings of the …, 1999 - National Acad Sciences
SH Cheshier, SJ Morrison, X Liao, IL Weissman
Proceedings of the National Academy of Sciences, 1999National Acad Sciences
A rare set of hematopoietic stem cells (HSC) must undergo a massive expansion to produce
mature blood cells. The phenotypic isolation of HSC from mice offers the opportunity to
determine directly their proliferation kinetics. We analyzed the proliferation and cell cycle
kinetics of long-term self-renewing HSC (LT-HSC) in normal adult mice. At any one time,≈
5% of LT-HSC were in S/G2/M phases of the cell cycle and another 20% were in G1 phase.
BrdUrd incorporation was used to determine the rate at which different cohorts of HSC …
A rare set of hematopoietic stem cells (HSC) must undergo a massive expansion to produce mature blood cells. The phenotypic isolation of HSC from mice offers the opportunity to determine directly their proliferation kinetics. We analyzed the proliferation and cell cycle kinetics of long-term self-renewing HSC (LT-HSC) in normal adult mice. At any one time, ≈5% of LT-HSC were in S/G2/M phases of the cell cycle and another 20% were in G1 phase. BrdUrd incorporation was used to determine the rate at which different cohorts of HSC entered the cell cycle over time. About 50% of LT-HSC incorporated BrdUrd by 6 days and >90% incorporated BrdUrd by 30 days. By 6 months, 99% of LT-HSC had incorporated BrdUrd. We calculated that approximately 8% of LT-HSC asynchronously entered the cell cycle per day. Nested reverse transcription–PCR analysis revealed cyclin D2 expression in a high proportion of LT-HSC. Although ≈75% of LT-HSC are quiescent in G0 at any one time, all HSC are recruited into cycle regularly such that 99% of LT-HSC divide on average every 57 days.
National Acad Sciences