Cheshier, Samuel H. and Morrison, Sean J. and Liao, Xinsheng and Weissman, Irving L. (1999) In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 96 (6). pp. 3120-3125. ISSN 0027-8424 http://resolver.caltech.edu/CaltechAUTHORS:CHEpnas99c
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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.
|Additional Information:||Copyright © 1999 by the National Academy of Sciences. Contributed by Irving L. Weissman, December 31, 1998. We thank Annete Schlageter, Jos Domen, Douglas Wright, Andrew BitMansour, and Dennise Dalma-Weiszhausz for critical review and help in preparing this manuscript. We also thank Libuse Jerabek, Veronica Braunstein, and Joe Verdi for antibodies and experimental expertise and Lucindo Hidalgo for animal care. This work was supported by USDH8 National Cancer Institute Grant CA-42551 to I.W.; S.H.C. was supported by the Medical Scientist Training Program Grant 5T32GM07365 at Stanford University School of Medicine. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.|
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