SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer.
10.1007/s13238-020-00728-4
- Author:
Shijia BI
1
;
Zunpeng LIU
1
;
Zeming WU
1
;
Zehua WANG
1
;
Xiaoqian LIU
1
;
Si WANG
2
;
Jie REN
3
;
Yan YAO
4
;
Weiqi ZHANG
5
;
Moshi SONG
6
;
Guang-Hui LIU
7
;
Jing QU
8
Author Information
1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
2. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
3. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
4. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
5. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. zhangwq@big.ac.cn.
6. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. songmoshi@ioz.ac.cn.
7. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ioz.ac.cn.
8. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn.
- Publication Type:Journal Article
- Keywords:
LINE1;
SIRT7;
STING;
aging;
cGAS;
stem cell
- From:
Protein & Cell
2020;11(7):483-504
- CountryChina
- Language:English
-
Abstract:
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, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These aging-associated 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.
