Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells
Liang Yue, Yangli Pei, Liang Zhong, Henry Yang, Yanliang Wang, Wei Zhang, Naixin Chen, Qianqian Zhu, Jie Gao, Minglei Zhi, Bingqiang Wen, Shaopeng Zhang, Jinzhu Xiang, Qingqing Wei, Hui Liang, Suying Cao, Huiqiang Lou, Zhongzhou Chen, Jianyong Han
Abstract
-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.