DNA Damage Response in Hematopoietic Stem Cell Ageing.
DNA Damage Response in Hematopoietic Stem Cell Ageing.
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造血干细胞衰老中的DNA损伤反应
DOI：
10.1016/j.gpb.2016.04.002
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Wang ZQ
中科院分区：
文献类型：
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作者：
Li T;Zhou ZW;Ju Z;Wang ZQ
组织特异性干细胞的维持对于器官稳态和生物体寿命至关重要。造血干细胞（HSCs）是造血系统中最原始的细胞类型。它们不对称分裂并产生具有HSC身份的子细胞（自我更新）和祖细胞后代（分化），其进一步增殖并分化成完整的造血谱系。哺乳动物的衰老过程伴随着HSC自我更新和分化的异常。转录变化和表观遗传调节是HSC衰老过程中的关键调控因子。细胞中的DNA损伤反应（DDR）涉及一个精心策划的信号通路，包括细胞周期调节、细胞死亡和衰老、转录调节以及染色质重塑。最近的研究采用DNA修复缺陷的小鼠模型表明，DDR可以内在和外在地调节HSC的维持，并在造血系统的组织稳态中发挥重要作用。在这篇综述中，我们总结了目前的理解如何DDR决定HSC的命运，并最终有助于生物体衰老。
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.