title: DNA Damage Response in Hematopoietic Stem Cell Ageing.
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.
authors.affiliation: Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China. Electronic address: li.tangliang@hznu.edu.cn.
authors.forename: Tangliang
authors.initials: T
authors.lastname: Li
authors.affiliation: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena D-07745, Germany.
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Zhou
authors.affiliation: Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ju
authors.affiliation: 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.
authors.forename: Zhao-Qi
authors.initials: ZQ
authors.lastname: Wang
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D016922:Cellular Senescence; D042002:Chromatin Assembly and Disassembly; D004249:DNA Damage; D004260:DNA Repair; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53
keywords: Ageing; DNA damage response; Epigenetics; Hematopoietic stem cells; P53