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Nat Cell Biol. 2013 Mar;15(3):309-16. doi: 10.1038/ncb2699. Epub 2013 Feb 24.

Nrf2 regulates haematopoietic stem cell function.

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1
Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.

Abstract

Coordinating the balance between haematopoietic stem cell (HSC) quiescence and self-renewal is crucial for maintaining haematopoiesis lifelong. Equally important for haematopoietic function is modulating HSC localization within the bone marrow niches, as maintenance of HSC function is tightly controlled by a complex network of intrinsic molecular mechanisms and extrinsic signalling interactions with their surrounding microenvironment. In this study we demonstrate that nuclear factor erythroid 2-related factor 2 (Nfe2l2, or Nrf2), well established as a global regulator of the oxidative stress response, plays a regulatory role in several aspects of HSC homeostasis. Nrf2 deficiency results in an expansion of the haematopoietic stem and progenitor cell compartment due to cell-intrinsic hyperproliferation, which was accomplished at the expense of HSC quiescence and self-renewal. We further show that Nrf2 modulates both migration and retention of HSCs in their niche. Moreover, we identify a previously unrecognized link between Nrf2 and CXCR4, contributing, at least partially, to the maintenance of HSC function.

PMID:
23434824
PMCID:
PMC3699879
DOI:
10.1038/ncb2699
[Indexed for MEDLINE]
Free PMC Article
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