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- Title
Nrf2 regulates haematopoietic stem cell function.
- Authors
Tsai, Jennifer J.; Dudakov, Jarrod A.; Takahashi, Koichi; Shieh, Jae-Hung; Velardi, Enrico; Holland, Amanda M.; Singer, Natalie V.; West, Mallory L.; Smith, Odette M.; Young, Lauren F.; Shono, Yusuke; Ghosh, Arnab; Hanash, Alan M.; Tran, Hien T.; Moore, Malcolm A. S.; van den Brink, Marcel R. M.
- 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.
- Subjects
HEMATOPOIETIC stem cells; LEUCINE zippers; HEMATOPOIESIS; BONE marrow; OXIDATIVE stress; BLOOD cells
- Publication
Nature Cell Biology, 2013, Vol 15, Issue 3, p309
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb2699