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Haematopoiesis

Keeping HSCs under control

Nature Reviews Immunology volume 4, page 834 (2004)Cite this article

GFI1 has previously been shown to promote T-cell proliferation. So, because GFI1 is expressed by HSCs, both groups set out to investigate whether it also promotes proliferation of these cells. Surprisingly, Hock et al. observed that, compared with wild-type litter–mate controls, there were at least as many, if not more, phenotypic HSCs in the bone marrow of GFI1-deficient mice. By contrast, Zeng et al. observed that the number of phenotypic HSCs was decreased in the bone marrow of GFI1-deficient mice. However, both groups showed that HSC function was compromised; when lethally irradiated mice were transplanted with a mixture of GFI1-deficient bone marrow and wild-type bone marrow, GFI1-deficient HSCs were outcompeted as the mice aged, and haematopoietic cells derived from the GFI1-deficient bone marrow were undetectable. Together with the observation that bone marrow from recipients of GFI1-deficient bone marrow was unable to reconstitute a secondary lethally irradiated recipient in a serial-transplantation assay, these results establish that GFI1 is crucial for HSC self-renewal and engraftment function.

Further analysis indicated that a larger proportion of GFI1-deficient bone-marrow HSCs were in the proliferative stages of the cell cycle, indicating that GFI1 functions to restrain HSC proliferation. Consistent with this proposed role for GFI1 in controlling proliferation and cell-cycle progression of HSCs, the level of mRNA encoding the G1 checkpoint regulator p21 (also known as CIP1 or WAF1), which is required to maintain HSCs in G0, was found to be decreased in GFI1-deficient HSCs.

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ORIGINAL RESEARCH PAPERS

  1. Hock, H. et al. Gfi-1 restricts proliferation and preserves functional integrity of haematopoeitc stem cells. Nature 431, 1002–1007 (2004).

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  2. Zeng, H., Yücel, R., Kosan, C., Klein-Hitpass, L. & Möröy, T. Transcription factor Gfi-1 regulates self-renewal and engraftment of haematopoietic stem cells. EMBO J. 23 September 2004 (doi:10.1038/sj.emboj.7600419).

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Authors
  1. Karen Honey
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Honey, K. Keeping HSCs under control. Nat Rev Immunol 4, 834 (2004). https://doi.org/10.1038/nri1495

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  • DOI: https://doi.org/10.1038/nri1495

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