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

Samuel H. Cheshier, Sean J. Morrison, Xinsheng Liao, Irving L. Weissman

Research output: Contribution to journalArticle

585 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3120-3125
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number6
DOIs
StatePublished - Mar 16 1999

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Hematopoietic Stem Cells
Cell Cycle
Cyclin D2
G2 Phase
G1 Phase
Cell Division
Reverse Transcription
Blood Cells
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. / Cheshier, Samuel H.; Morrison, Sean J.; Liao, Xinsheng; Weissman, Irving L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 6, 16.03.1999, p. 3120-3125.

Research output: Contribution to journalArticle

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