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

A rare set of hematopoietic stem cells (HSC) must undergo a massive expansi on 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 long-term self-renew ing HSC (LT-HSC) in normal adult mice, ht any one time, approximate to 5% o f LT-HSC were in S/G(2)/M phases of the cell cycle and another 20% were in G(1) phase. BrdUrd incorporation was used to determine the rate at which di fferent cohorts of HSC entered the cell cycle over time. About 50% of LT-HS C incorporated BrdUrd by 6 days and >90% incorporated BrdUrd by 30 days, By 6 months, 99% of LT-I-ISC had incorporated BrdUrd. We calculated that appr oximately 8% of LT-BSC asynchronously entered the cell cycle per day. Neste d reverse transcription-PCR analysis revealed cyclin D2 expression in a hig h proportion of LT-BSC. Although approximate to 75% of LT-HSC are quiescent in G(0) at any one time, all HSC are recruited into cycle regularly such t hat 99% of LT-HSC divide on average every 57 days.