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Metabolic and cell cycle shift induced by the deletion of Dnm1l attenuates the dissolution of pluripotency in mouse embryonic stem cells

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Abstract

Mitochondria are versatile organelles that continuously change their morphology via fission and fusion. However, the detailed functions of mitochondrial dynamics-related genes in pluripotent stem cells remain largely unclear. Here, we aimed to determine the effects on energy metabolism and differentiation ability of mouse embryonic stem cells (ESCs) following deletion of the mitochondrial fission-related gene Dnml1. Resultant Dnm1l−/− ESCs maintained major pluripotency characteristics. However, Dnm1l−/− ESCs showed several phenotypic changes, including the inhibition of differentiation ability (dissolution of pluripotency). Notably, Dnm1l−/− ESCs maintained the expression of the pluripotency marker Oct4 and undifferentiated colony types upon differentiation induction. RNA sequencing analysis revealed that the most frequently differentially expressed genes were enriched in the glutathione metabolic pathway. Our data suggested that differentiation inhibition of Dnm1l−/− ESCs was primarily due to metabolic shift from glycolysis to OXPHOS, G2/M phase retardation, and high level of Nanog and 2-cell-specific gene expression.

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Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) of the Republic of Korea (Grant No. RS-2023-00208330) and the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET), funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA) (Grant No. 322006-05-02-CG000).

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Authors and Affiliations

  1. Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, Seoul, 05029, Republic of Korea

    Bong Jong Seo, Seung Bin Na, Joonhyuk Choi, Byeongyong Ahn, Chankyu Park, Kwonho Hong & Jeong Tae Do

  2. Department of Chemistry, Hanyang University, Seoul, 04763, Republic of Korea

    Omer Habib

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  1. Bong Jong Seo
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  2. Seung Bin Na
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Contributions

BJS and JTD: wrote the main manuscript and designed the study. BJS, SBN, and JC: performed experiments and analyzed data. BJS, BA, CP, KH, and JTD: performed data analysis. All authors reviewed the manuscript.

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Correspondence to Jeong Tae Do.

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Seo, B.J., Na, S.B., Choi, J. et al. Metabolic and cell cycle shift induced by the deletion of Dnm1l attenuates the dissolution of pluripotency in mouse embryonic stem cells. Cell. Mol. Life Sci. 80, 302 (2023). https://doi.org/10.1007/s00018-023-04962-x

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