Nrf2 Regulates Haematopoietic Stem Cell Function

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2013 Feb 26

PMID 23434824

Citations 121

Authors

Jennifer J Tsai

Jarrod A Dudakov

Koichi Takahashi

Jae-Hung Shieh

Enrico Velardi

Amanda M Holland

Natalie V Singer

Mallory L West

Odette M Smith

Lauren F Young

Yusuke Shono

Arnab Ghosh

Alan M Hanash

Hien T Tran

Malcolm A S Moore

Marcel R M van den Brink

Affiliations

Soon will be listed here.

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.

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