SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer

doi:10.1007/s13238-020-00728-4

Protein Cell

2020, Vol. 11

Issue (7) : 483-504 https://doi.org/10.1007/s13238-020-00728-4

RESEARCH ARTICLE

SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer

Shijia Bi^1,⁷, Zunpeng Liu^1,⁷, Zeming Wu^1,⁷, Zehua Wang^1,⁷, Xiaoqian Liu^1,⁷, Si Wang^2,^3,^6,⁷, Jie Ren^4,^5,^6,⁷, Yan Yao⁸, Weiqi Zhang^4,^5,^6,⁷(

), Moshi Song^2,^6,⁷(

), Guang-Hui Liu^2,^3,^6,⁷(

), Jing Qu^1,^6,⁷(

)

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. Beijing 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, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
⁵. China National Center for Bioinformation, Beijing 100101, China
⁶. Institute for Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
⁷. University of Chinese Academy of Sciences, Beijing 100049, China
⁸. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China

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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 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.

Keywords SIRT7 stem cell aging LINE1 cGAS STING

Corresponding Author(s): Weiqi Zhang,Moshi Song,Guang-Hui Liu,Jing Qu

Issue Date: 31 July 2020

Cite this article:

Shijia Bi,Zunpeng Liu,Zeming Wu, et al. SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer[J]. Protein Cell, 2020, 11(7): 483-504.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-020-00728-4
https://academic.hep.com.cn/pac/EN/Y2020/V11/I7/483

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