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DNA Damage Response in Hematopoietic Stem Cell Ageing.

Authors
  • Li, Tangliang1
  • Zhou, Zhong-Wei2
  • Ju, Zhenyu3
  • Wang, Zhao-Qi4
  • 1 Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China. Electronic address: [email protected] , (China)
  • 2 Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena D-07745, Germany. , (Germany)
  • 3 Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China. , (China)
  • 4 Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena D-07745, Germany; Faculty of Biology and Pharmacy, Friedrich-Schiller University of Jena, Jena D-07745, Germany. , (Germany)
Type
Published Article
Journal
Genomics, proteomics & bioinformatics
Publication Date
Jun 01, 2016
Volume
14
Issue
3
Pages
147–154
Identifiers
DOI: 10.1016/j.gpb.2016.04.002
PMID: 27221660
Source
Medline
Keywords
License
Unknown

Abstract

Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

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