International Journal of Hematology

DOI: 10.1007/s12185-011-0872-1 Pages: 24-32

Reactive oxygen species and hematopoietic stem cell senescence

1. University of Arkansas for Medical Sciences, Division of Radiation Health, Department of Pharmaceutical Sciences

2. Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Institute of Radiation Medicine

3. Medical University of South Carolina, Department of Pathology

4. University of Arkansas for Medical Sciences, Winthrop P. Rockefeller Cancer Institute

Correspondence to:
Daohong Zhou
Tel: +1-501-5265272
Fax: +1-501-6866517
Email: dzhou@uams.edu

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Abstract

Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic homeostasis and regeneration after injury for the entire lifespan of an organism through self-renewal, proliferation, differentiation, and mobilization. Their functions can be affected by reactive oxygen species (ROS) that are produced endogenously through cellular metabolism or after exposure to exogenous stress. At physiological levels, ROS function as signal molecules which can regulate a variety of cellular functions, including HSC proliferation, differentiation, and mobilization. However, an abnormal increase in ROS production occurs under various pathological conditions, which can inhibit HSC self-renewal and induce HSC senescence, resulting in premature exhaustion of HSCs and hematopoietic dysfunction. This review aims to provide a summary of a number of recent findings regarding the cellular sources of ROS in HSCs and the mechanisms of action whereby ROS induce HSC senescence. In particular, we highlight the roles of the p38 mitogen-activated protein kinase (p38)-p16Ink4a (p16) pathway in mediating ROS-induced HSC senescence.

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