Metabolic and cell cycle shift induced by the deletion of Dnm1l attenuates the dissolution of pluripotency in mouse embryonic stem cells
Year: 2023
Type: article
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.
Institutions: Konkuk University, Hanyang University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Research Foundation, Ministry of Agriculture, Food and Rural Affairs, Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries, National Research Foundation of Korea, Ministry of Science and ICT, South Korea, Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry
OpenAlex ID: W4387002597