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Telomere dysfunction and cell cycle checkpoints in hematopoietic stem cell aging

  • Progress in Hematology
  • Hematopoietic stem cell aging
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Stem cells are believed to be closely associated with tissue degeneration during aging. Studies of human genetic diseases and gene-targeted animal models have provided evidence that functional decline of telomeres and deregulation of cell cycle checkpoints contribute to the aging process of tissue stem cells. Telomere dysfunction can induce DNA damage response via key cell cycle checkpoints, leading to cellular senescence or apoptosis depending on the tissue type and developmental stage of a specific stem cell compartment. Telomerase mutation and telomere shortening have been observed in a variety of hematological disorders, such as dyskeratosis congenital, aplastic anemia, myelodysplastic syndromes and leukemia, in which the hematopoietic stem cells (HSC) are a major target during the pathogenesis. Moreover, telomere dysfunction is able to induce both cell-intrinsic checkpoints and environmental factors limiting the self-renewal capacity and differentiation potential of HSCs. Crucial components in the cascade of DNA damage response, including ataxia telangiectasia mutated, CHK2, p53, p21 and p16/p19ARF, play important roles in HSC maintenance and self-renewal in the scenarios of both sufficient telomere reserve and dysfunctional telomere. Therefore, a further understanding of the molecular mechanisms underlying HSC aging may help identity new therapeutic targets for stem cell-based regenerative medicine.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (NSFC; 81090410), the National Basic Research Program of China (2011CB964800) and the National Science Fund for Outstanding Young Scholars (30825017).

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Authors and Affiliations

  1. School of Medicine, Hangzhou Normal University, Hangzhou, China

    Zhenyu Ju

  2. Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin, China

    Junling Zhang

  3. State Key Laboratory of Experimental Hematology, Institute of Hematology and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Tianjin, China

    Yingdai Gao & Tao Cheng

  4. Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Tao Cheng

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  1. Zhenyu Ju
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  2. Junling Zhang
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  3. Yingdai Gao
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  4. Tao Cheng
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Correspondence to Zhenyu Ju or Tao Cheng.

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Ju, Z., Zhang, J., Gao, Y. et al. Telomere dysfunction and cell cycle checkpoints in hematopoietic stem cell aging. Int J Hematol 94, 33–43 (2011). https://doi.org/10.1007/s12185-011-0882-z

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  • DOI: https://doi.org/10.1007/s12185-011-0882-z

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