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Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells

The pluripotency of stem cells determines their developmental potential. While the pluripotency states of pluripotent stem cells are variable and interconvertible, the mechanisms underlying the acquisition and maintenance of pluripotency remain largely elusive. Here, we identified that methylenetetr...

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Detalles Bibliográficos
Autores principales: Yue, Liang, Pei, Yangli, Zhong, Liang, Yang, Henry, Wang, Yanliang, Zhang, Wei, Chen, Naixin, Zhu, Qianqian, Gao, Jie, Zhi, Minglei, Wen, Bingqiang, Zhang, Shaopeng, Xiang, Jinzhu, Wei, Qingqing, Liang, Hui, Cao, Suying, Lou, Huiqiang, Chen, Zhongzhou, Han, Jianyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419720/
https://www.ncbi.nlm.nih.gov/pubmed/32679066
http://dx.doi.org/10.1016/j.stemcr.2020.06.018
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author Yue, Liang
Pei, Yangli
Zhong, Liang
Yang, Henry
Wang, Yanliang
Zhang, Wei
Chen, Naixin
Zhu, Qianqian
Gao, Jie
Zhi, Minglei
Wen, Bingqiang
Zhang, Shaopeng
Xiang, Jinzhu
Wei, Qingqing
Liang, Hui
Cao, Suying
Lou, Huiqiang
Chen, Zhongzhou
Han, Jianyong
author_facet Yue, Liang
Pei, Yangli
Zhong, Liang
Yang, Henry
Wang, Yanliang
Zhang, Wei
Chen, Naixin
Zhu, Qianqian
Gao, Jie
Zhi, Minglei
Wen, Bingqiang
Zhang, Shaopeng
Xiang, Jinzhu
Wei, Qingqing
Liang, Hui
Cao, Suying
Lou, Huiqiang
Chen, Zhongzhou
Han, Jianyong
author_sort Yue, Liang
collection PubMed
description The pluripotency of stem cells determines their developmental potential. While the pluripotency states of pluripotent stem cells are variable and interconvertible, the mechanisms underlying the acquisition and maintenance of pluripotency remain largely elusive. Here, we identified that methylenetetrahydrofolate dehydrogenase (NAD(+)-dependent), methenyltetrahydrofolate cyclohydrolase (Mthfd2) plays an essential role in maintaining embryonic stem cell pluripotency and promoting complete reprogramming of induced pluripotent stem cells. Mechanistically, in mitochondria, Mthfd2 maintains the integrity of the mitochondrial respiratory chain and prevents mitochondrial dysfunction. In the nucleus, Mthfd2 stabilizes the phosphorylation of EXO1 to support DNA end resection and promote homologous recombination repair. Our results revealed that Mthfd2 is a dual-function factor in determining the pluripotency of pluripotent stem cells through both mitochondrial and nuclear pathways, ultimately ensuring safe application of pluripotent stem cells.
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spelling pubmed-74197202020-08-14 Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells Yue, Liang Pei, Yangli Zhong, Liang Yang, Henry Wang, Yanliang Zhang, Wei Chen, Naixin Zhu, Qianqian Gao, Jie Zhi, Minglei Wen, Bingqiang Zhang, Shaopeng Xiang, Jinzhu Wei, Qingqing Liang, Hui Cao, Suying Lou, Huiqiang Chen, Zhongzhou Han, Jianyong Stem Cell Reports Article The pluripotency of stem cells determines their developmental potential. While the pluripotency states of pluripotent stem cells are variable and interconvertible, the mechanisms underlying the acquisition and maintenance of pluripotency remain largely elusive. Here, we identified that methylenetetrahydrofolate dehydrogenase (NAD(+)-dependent), methenyltetrahydrofolate cyclohydrolase (Mthfd2) plays an essential role in maintaining embryonic stem cell pluripotency and promoting complete reprogramming of induced pluripotent stem cells. Mechanistically, in mitochondria, Mthfd2 maintains the integrity of the mitochondrial respiratory chain and prevents mitochondrial dysfunction. In the nucleus, Mthfd2 stabilizes the phosphorylation of EXO1 to support DNA end resection and promote homologous recombination repair. Our results revealed that Mthfd2 is a dual-function factor in determining the pluripotency of pluripotent stem cells through both mitochondrial and nuclear pathways, ultimately ensuring safe application of pluripotent stem cells. Elsevier 2020-07-16 /pmc/articles/PMC7419720/ /pubmed/32679066 http://dx.doi.org/10.1016/j.stemcr.2020.06.018 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Yue, Liang
Pei, Yangli
Zhong, Liang
Yang, Henry
Wang, Yanliang
Zhang, Wei
Chen, Naixin
Zhu, Qianqian
Gao, Jie
Zhi, Minglei
Wen, Bingqiang
Zhang, Shaopeng
Xiang, Jinzhu
Wei, Qingqing
Liang, Hui
Cao, Suying
Lou, Huiqiang
Chen, Zhongzhou
Han, Jianyong
Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells
title Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells
title_full Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells
title_fullStr Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells
title_full_unstemmed Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells
title_short Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells
title_sort mthfd2 modulates mitochondrial function and dna repair to maintain the pluripotency of mouse stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419720/
https://www.ncbi.nlm.nih.gov/pubmed/32679066
http://dx.doi.org/10.1016/j.stemcr.2020.06.018
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