Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells

William Fleming, Eytan J. Alpern, Nobuko Uchida, Koichi Ikuta, Gerald J. Spangrude, Irving L. Weissman

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

Hematopoietic stem cells (HSCs) are characterized by their ability to differentiate into all hematopoietic cell lineages while retaining their capacity for self renewal. One of the predictions of this model is the existence of a heterogeneous pool of HSCs, some members of which are destined to become lineage restricted progenitor cells while others function to renew the stem cell pool. To test whether HSCs are heterogeneous with respect to cell cycle status, we determined the fraction of phenotypically defined murine HSCs (Thy 1.1lo Lin-/lo Sca-1+) that contain >2n amount of DNA as measured by propidium iodide staining, Hoechst dye uptake and [3H]thymidine labeling; that fraction is 18-22%. In contrast, in the developing fetal liver, 40% of HSCs are in the S/G2/M phases of the cell cycle. Those HSCs which exhibit a low level of staining with rhodamine 123 are almost exclusively in GO/G1 (97%) whereas only 70% of HSCs which stain brightly for rhodamine 123 are in GO/G1. The injection of 100 GO/G1 HSCs rescued 90% of lethally irradiated mice in contrast to 100 S/G2/M HSCs, which protected only 25% of lethally irradiated recipients. Enhanced long-term donorderived multilineage reconstitution of the peripheral blood was observed in recipients of 100 GO/G1 HSCs compared to recipients of 100 S/G2/M cells. These data indicate that a significant proportion of HSCs are actively proliferating during steady state hematopoiesis and that this subpopulation of cells exhibits reduced stem cell activity.

Original languageEnglish (US)
Pages (from-to)897-902
Number of pages6
JournalJournal of Cell Biology
Volume122
Issue number4
StatePublished - Aug 1993
Externally publishedYes

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Hematopoietic Stem Cells
Cell Cycle
Rhodamine 123
Stem Cells
Coloring Agents
Staining and Labeling
Propidium
G2 Phase
Hematopoiesis
Cell Lineage
Cell Division
Thymidine
Injections
Liver

ASJC Scopus subject areas

  • Cell Biology

Cite this

Fleming, W., Alpern, E. J., Uchida, N., Ikuta, K., Spangrude, G. J., & Weissman, I. L. (1993). Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells. Journal of Cell Biology, 122(4), 897-902.

Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells. / Fleming, William; Alpern, Eytan J.; Uchida, Nobuko; Ikuta, Koichi; Spangrude, Gerald J.; Weissman, Irving L.

In: Journal of Cell Biology, Vol. 122, No. 4, 08.1993, p. 897-902.

Research output: Contribution to journalArticle

Fleming, W, Alpern, EJ, Uchida, N, Ikuta, K, Spangrude, GJ & Weissman, IL 1993, 'Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells', Journal of Cell Biology, vol. 122, no. 4, pp. 897-902.
Fleming, William ; Alpern, Eytan J. ; Uchida, Nobuko ; Ikuta, Koichi ; Spangrude, Gerald J. ; Weissman, Irving L. / Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells. In: Journal of Cell Biology. 1993 ; Vol. 122, No. 4. pp. 897-902.
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