首页|MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer

MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer

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Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ aging.Here,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also regulates human stem cell senescence.To answer this question,we used CRISPR/Cas9-mediated gene editing and directed differentiation techniques to generate various MAVS-knockout human stem cell models.We found that human mesenchymal stem cells(hMSCs)were sensitive to MAVS deficiency,as manifested by accelerated senescence phenotypes.We uncovered that the role of MAVS in maintaining mitochondrial structural integrity and functional homeostasis depends on its interaction with the guanosine triphosphatase optic atrophy type 1(OPA1).Depletion of MAVS or OPA1 led to the dysfunction of mitochondria and cellular senescence,whereas replenishment of MAVS or OPA1 in MAVS-knockout hMSCs alleviated mitochondrial defects and premature senescence phenotypes.Taken together,our data underscore an uncanonical role of MAVS in safeguarding mitochondrial homeostasis and antagonizing human stem cell senescence.

Cui Wang、Kuan Yang、Xiaoqian Liu、Si Wang、Moshi Song、Juan Carlos Izpisua Belmonte、Jing Qu、Guang-Hui Liu、Weiqi Zhang

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CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China

University of Chinese Academy of Sciences,Beijing 100049,China

Sino-Danish College,University of Chinese Academy of Sciences,Beijing 101408,China

State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China

Institute for Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China

Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China

Advanced Innovation Center for Human Brain Protection,National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China

State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China

Altos Labs,Inc.,San Diego,CA 94022,USA

State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101

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National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaStrategic Priority Research Program of the Chinese Academy of SciencesCAS Project for Young Scientists in Basic ResearchCAS Project for Young Scientists in Basic ResearchProgram of the Beijing Natural Science FoundationYouth Innovation Promotion Association of CASPilot Project for Public Welfare Development and Reform of Beijingaffiliated Medical Research InstitutesInformatization Plan of Chinese Academy of SciencesInformatization Plan of Chinese Academy of SciencesInformatization Plan of Chinese Academy of SciencesYoung Elite Scientists Sponsorship Program by CASTNew Cornerstone Science Foundation through the XPLORER PRIZEExcellent Young Talents Program of Capital Medical UniversityExcellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team

2022YFA11037002020YFA-08040002020YFA01122002021YFF1201005the STI2030-Major Projects-2021ZD02024008192100682125011921493019216820191949209920493049204911632121001821928638212202482071588XDA16000000YSBR-076YSBR-012Z190019E1CAZW040111000022T0000-00461062CAS-WX2021SF-0101CAS-WX2021SF-0301CAS-WX2022SDC-XK14YESS202000122021-104512300927BPHR202203105

2024

10.34133/research.0192

研究(英文)

研究(英文)

CSTPCD
ISSN：
年,卷(期)：2024.2024(2)
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