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Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells

Author

Listed:
  • In-kyung Park

    (University of Michigan)

  • Dalong Qian

    (University of Michigan)

  • Mark Kiel

    (University of Michigan)

  • Michael W. Becker

    (University of Michigan)

  • Michael Pihalja

    (University of Michigan)

  • Irving L. Weissman

    (Stanford University)

  • Sean J. Morrison

    (University of Michigan)

  • Michael F. Clarke

    (University of Michigan)

Abstract

A central issue in stem cell biology is to understand the mechanisms that regulate the self-renewal of haematopoietic stem cells (HSCs), which are required for haematopoiesis to persist for the lifetime of the animal1. We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. The number of HSCs in the fetal liver of Bmi-1-/- mice2 was normal. In postnatal Bmi-1-/- mice, the number of HSCs was markedly reduced. Transplanted fetal liver and bone marrow cells obtained from Bmi-1-/- mice were able to contribute only transiently to haematopoiesis. There was no detectable self-renewal of adult HSCs, indicating a cell autonomous defect in Bmi-1-/- mice. A gene expression analysis revealed that the expression of stem cell associated genes3, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice. Expression of p16Ink4a and p19Arf in normal HSCs resulted in proliferative arrest and p53-dependent cell death, respectively. Our results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs.

Suggested Citation

  • In-kyung Park & Dalong Qian & Mark Kiel & Michael W. Becker & Michael Pihalja & Irving L. Weissman & Sean J. Morrison & Michael F. Clarke, 2003. "Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells," Nature, Nature, vol. 423(6937), pages 302-305, May.
    • Handle: RePEc:nat:nature:v:423:y:2003:i:6937:d:10.1038_nature01587
    DOI: 10.1038/nature01587
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