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International Journal of Hematology

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01.07.2011 | Progress in Hematology

Telomere dysfunction and cell cycle checkpoints in hematopoietic stem cell aging

verfasst von: Zhenyu Ju, Junling Zhang, Yingdai Gao, Tao Cheng

Erschienen in: International Journal of Hematology | Ausgabe 1/2011

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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/p19^ARF, 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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Titel: Telomere dysfunction and cell cycle checkpoints in hematopoietic stem cell aging
verfasst von: Zhenyu Ju
Junling Zhang
Yingdai Gao
Tao Cheng
Publikationsdatum: 01.07.2011
Verlag: Springer Japan
Erschienen in: International Journal of Hematology / Ausgabe 1/2011
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-011-0882-z

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Telomere dysfunction and cell cycle checkpoints in hematopoietic stem cell aging

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