Nrf2 regulates haematopoietic stem cell function Academic Article uri icon

Overview

MeSH Major

  • Bone Marrow
  • Cell Communication
  • Cell Proliferation
  • Hematopoiesis
  • Hematopoietic Stem Cells
  • NF-E2-Related Factor 2
  • Stromal Cells

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.

publication date

  • March 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3699879

Digital Object Identifier (DOI)

  • 10.1038/ncb2699

PubMed ID

  • 23434824

Additional Document Info

start page

  • 309

end page

  • 16

volume

  • 15

number

  • 3