MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer
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/C...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2023-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0192 |
| _version_ | 1797280283952676864 |
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| author | Cui Wang Kuan Yang Xiaoqian Liu Si Wang Moshi Song Juan Carlos Izpisua Belmonte Jing Qu Guang-Hui Liu Weiqi Zhang |
| author_facet | Cui Wang Kuan Yang Xiaoqian Liu Si Wang Moshi Song Juan Carlos Izpisua Belmonte Jing Qu Guang-Hui Liu Weiqi Zhang |
| author_sort | Cui Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T16:37:56Z |
| format | Article |
| id | doaj.art-f8170dcb559846219f80d4f332273368 |
| institution | Directory Open Access Journal |
| issn | 2639-5274 |
| language | English |
| last_indexed | 2024-03-07T16:37:56Z |
| publishDate | 2023-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj.art-f8170dcb559846219f80d4f3322733682024-03-03T09:36:59ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742023-01-01610.34133/research.0192MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial StabilizerCui Wang0Kuan Yang1Xiaoqian Liu2Si Wang3Moshi Song4Juan Carlos Izpisua Belmonte5Jing Qu6Guang-Hui Liu7Weiqi Zhang8CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China.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.State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 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.University of Chinese Academy of Sciences, Beijing 100049, China.Altos Labs, Inc., San Diego, CA 94022, USA.University of Chinese Academy of Sciences, Beijing 100049, China.University of Chinese Academy of Sciences, Beijing 100049, China.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.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.https://spj.science.org/doi/10.34133/research.0192 |
| spellingShingle | Cui Wang Kuan Yang Xiaoqian Liu Si Wang Moshi Song Juan Carlos Izpisua Belmonte Jing Qu Guang-Hui Liu Weiqi Zhang MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer Research |
| title | MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer |
| title_full | MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer |
| title_fullStr | MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer |
| title_full_unstemmed | MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer |
| title_short | MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer |
| title_sort | mavs antagonizes human stem cell senescence as a mitochondrial stabilizer |
| url | https://spj.science.org/doi/10.34133/research.0192 |
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