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Reactive oxygen species and hematopoietic stem cell senescence

  • Progress in Hematology
  • Hematopoietic stem cell aging
  • Published:
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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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Acknowledgments

This study was supported in part by grants from the National Institutes of Health (R01-CA086688, CA102558, and AI080421), and a grant from the National Natural Science Foundation of China (NSFC 30828011), the Winthrop Rockefeller Endowment for Leukemia Research, and the Arkansas Research Alliance Scholarship from the Arkansas Science & Technology Authority.

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Authors and Affiliations

  1. Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Lijian Shao, Hongliang Li, Senthil K. Pazhanisamy & Daohong Zhou

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

    Hongliang Li & Aimin Meng

  3. Department of Pathology, Medical University of South Carolina, Charleston, SC, USA

    Yong Wang

  4. Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 W Markham, #607, Little Rock, AR, 72205, USA

    Daohong Zhou

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  1. Lijian Shao
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  2. Hongliang Li
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  5. Yong Wang
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Correspondence to Daohong Zhou.

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Shao, L., Li, H., Pazhanisamy, S.K. et al. Reactive oxygen species and hematopoietic stem cell senescence. Int J Hematol 94, 24–32 (2011). https://doi.org/10.1007/s12185-011-0872-1

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