论文
论文题目: SIRT3 consolidates heterochromatin and counteracts senescence
论文题目英文:
作者: Diao,Zhiqing;Ji,Qianzhao;Wu,Zeming;Zhang,Weiqi;Cai,Yusheng;Wang,Zehua;Hu,Jianli;Liu,Zunpeng;Wang,Qiaoran;Bi,Shijia;Huang,Daoyuan;Ji,Zhejun;Liu,Guang-Hui;Wang,Si;Song,Moshi;Qu,Jing
论文出处:
年: 2021
卷: 49
期: 8
页: 4203-4219
联系作者: 曲静
发表期刊: Nucleic Acids Research
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论文连接 http://academic-oup-com-s.webvpn.ioz.ac.cn/nar/advance-article/doi/10.1093/nar/gkab161/6168313
影响因子: 19.16
摘要: Sirtuin 3 (SIRT3) is an NAD(+)-dependent deacetylase linked to a broad range of physiological and pathological processes, including aging and aging-related diseases. However, the role of SIRT3 in regulating human stem cell homeostasis remains unclear. Here we found that SIRT3 expression was downregulated in senescent human mesenchymal stem cells (hMSCs). CRISPR/Cas9-mediated depletion of SIRT3 led to compromised nuclear integrity, loss of heterochromatin and accelerated senescence in hMSCs. Further analysis indicated that SIRT3 interacted with nuclear envelope proteins and heterochromatin-associated proteins. SIRT3 deficiency resulted in the detachment of genomic lamina-associated domains (LADs) from the nuclear lamina, increased chromatin accessibility and aberrant repetitive sequence transcription. The re-introduction of SIRT3 rescued the disorganized heterochromatin and the senescence phenotypes. Taken together, our study reveals a novel role for SIRT3 in stabilizing heterochromatin and counteracting hMSC senescence, providing new potential therapeutic targets to ameliorate aging-related diseases.
英文摘要:
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