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Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14134-9. Epub 2006 Sep 12.

Hedgehog modulates cell cycle regulators in stem cells to control hematopoietic regeneration.

Author information

1
Department of Microbiology and Immunology, University of Western Ontario, 1151 Richmond Street, Suite 2, London, ON, Canada N6A 5B8.

Abstract

The signals that control the regenerative ability of hematopoietic stem cells (HSCs) in response to damage are unknown. Here, we demonstrate that downstream activation of the Hedgehog (Hh) signaling pathway induces cycling and expansion of primitive bone marrow hematopoietic cells under homeostatic conditions and during acute regeneration. However, this effect is at the expense of HSC function, because continued Hh activation during regeneration represses expression of specific cell cycle regulators, leading to HSC exhaustion. In vivo treatment with an inhibitor of the Hh pathway rescues these transcriptional and functional defects in HSCs. Our study establishes Hh signaling as a regulator of the HSC cell cycle machinery that balances hematopoietic homeostasis and regeneration in vivo.

PMID:
16968775
PMCID:
PMC1599924
DOI:
10.1073/pnas.0604568103
[Indexed for MEDLINE]
Free PMC Article

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