Hematopoietic stem cells(HSCs)replenish all lineages of blood cells throughout the lifespan.During aging,the repopulation capacity of HSCs declined,and aged HSCs display a tendency for myeloid differentiation.Several ...Hematopoietic stem cells(HSCs)replenish all lineages of blood cells throughout the lifespan.During aging,the repopulation capacity of HSCs declined,and aged HSCs display a tendency for myeloid differentiation.Several intrinsic and extrinsic factors have been identified to promote HSCs aging.In this review,we focus on the contribution of aging-associated inflammation in provoking HSCs aging and discuss the future research direction of inflammation and HSC aging.展开更多
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 asymmetricall...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.展开更多
基金This work was supported by grant numbers 2018YFA0800200,2017YFA0104000,Z181100001818005 and 91849106 to J.WW.,from the National KeyR&D Program of China or the Beijing Municipal Science&Technology Commission and the National Natural Science Foundation of China.
文摘Hematopoietic stem cells(HSCs)replenish all lineages of blood cells throughout the lifespan.During aging,the repopulation capacity of HSCs declined,and aged HSCs display a tendency for myeloid differentiation.Several intrinsic and extrinsic factors have been identified to promote HSCs aging.In this review,we focus on the contribution of aging-associated inflammation in provoking HSCs aging and discuss the future research direction of inflammation and HSC aging.
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)+2 种基金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
文摘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.
