DNA Damage Response in Hematopoietic Stem Cell Ageing  

作　　者：Tangliang Li Zhong-Wei Zhou Zhenyu Ju Zhao-Qi Wang 

机构地区：[1]Institute of Aging Research,School of Medicine,Hangzhou Normal University,Hangzhou 311121,China [2]Leibniz Institute on Aging-Fritz Lipmann Institute(FLI),Jena D-07745,Germany [3]Faculty of Biology and Pharmacy,Friedrich-Schiller University of Jena,Jena D-07745,Germany

出　　处：《Genomics, Proteomics & Bioinformatics》2016年第3期147-154,共8页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant No.81571380);the Natural Science Foundation of Zhejiang Province–China(Grant No.LY16H080009);supported by the National Natural Science Foundation of China(Grant Nos.81130074,81420108017,and 81525010);funded by the National Key R&D Plan from the Ministry of Science and Technology of China(Grant No.SQ2016ZY05002341);partially supported by the Deutsche Forschungsgemeinschaft(DFG),Germany

摘　　要：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.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.

关 键 词：Hematopoietic stem cells DNA damage response Epigenetics Ageing P53 

分 类 号：Q343[生物学—遗传学]