DNA Damage Response in Hematopoietic Stem Cell Ageing

• Published in: Genomics, proteomics & bioinformatics Vol. 14; no. 3; pp. 147 - 154
• Main Authors: Li, Tangliang, Zhou, Zhong-Wei, Ju, Zhenyu, Wang, Zhao-Qi
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.06.2016; Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China%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; Elsevier; Oxford University Press
• Subjects: Ageing; Animals; Cell Cycle Checkpoints; Cell Cycle Proteins - metabolism; Cell Differentiation; Cellular Senescence; Chromatin Assembly and Disassembly; DNA Damage; DNA damage response; DNA Repair; DNA损伤; Epigenetics; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; P53; Review; Signal Transduction; Tumor Suppressor Protein p53 - metabolism; 信号转导通路; 应答; 组织特异性; 细胞周期调控; 细胞老化; 造血干细胞; 造血系统; Epigenetics; DNA damage response; Ageing; Hematopoietic stem cells; P53
• ISSN: 1672-0229; 2210-3244
• DOI: 10.1016/j.gpb.2016.04.002

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（selfrenewal） 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.