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

Stem Cell Reports
Liang YueJianyong Han

Abstract

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.

Citations

Dec 15, 2020·Drug Discovery Today·Chengcan YangLiang Ouyang
Jun 15, 2021·Journal of Cellular and Molecular Medicine·Yangfeng ShiKejing Ying
Jul 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Gen LiPeng Jiang

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Datasets Mentioned

BETA
SRP149554

Methods Mentioned

BETA
Assay
CoIP
pull-down
immunoprecipitation
Flow-cytometry
RNA-seq
fluorescence-activated cell sorting

Software Mentioned

TMRE

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