SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer  

作　　者：Shijia Bi Zunpeng Liu Zeming Wu Zehua Wang Xiaoqian Liu Si Wang Jie Ren Yan Yao Weiqi Zhang Moshi Song Guang-Hui Liu Jing Qu 

机构地区：[1]State Key Laboratory of Stem Cell and Reproductive Biology,Instiute of Zoology,Chinese Academy of Sciences,Bejing 100101,China [2]State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Bejing 100101,China [3]Beiing Institute for Brain Disorders,Advanced Innovation Center for Human Brain Protection,National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China [4]CAS Key Laboratory of Genomic and Precision Medicine,Beiing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China [5]China National Center for Bioinformation,Bejing 100101,China [6]Institute for Stem cell and Regeneration,Chinese Academy of Sciences,Beiing 100101,China [7]University of Chinese Academy of Sciences,Beijing 100049,China [8]Department of Cardiology,Bejing Anzhen Hospital,Capital Medical University,Beijing 100029,China

出　　处：《Protein & Cell》2020年第7期483-504,共22页蛋白质与细胞（英文版）

摘　　要：SIRT7,a sirtuin family member implicated in aging and disease,is a regulator of metabolism and stress responses.It remains elusive how human somatic stem cell populations might be impacted by SIRT7.Here,we found that SIRT7 expression declines during human mesenchymal stem cell(hMSC)aging and that SIRT7 deficiency accelerates senescence.Mechanistically,SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins,thus maintaining the repressive state of heterochromatin at nuclear periphery.Accordingly,deficiency of SIRT7 results in loss of heterochromatin,derepression of the LINE1 retrotransposon(LINE1),and activation of innate immune signaling via the cGAS-STING pathway.These agingassociated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor.Together,these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.

关 键 词：SIRT7 stem cell AGING LINE1 cGAS STING 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]