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High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts.
- Source :
-
Cells [Cells] 2021 Aug 10; Vol. 10 (8). Date of Electronic Publication: 2021 Aug 10. - Publication Year :
- 2021
-
Abstract
- Mitochondria play a key role in metabolic transitions involved in the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), but the underlying molecular mechanisms remain largely unexplored. To obtain new insight into the mechanisms of cellular reprogramming, we studied the role of FAH domain-containing protein 1 (FAHD1) in the reprogramming of murine embryonic fibroblasts (MEFs) into iPSCs and their subsequent differentiation into neuronal cells. MEFs from wild type (WT) and Fahd1-knock-out (KO) mice were reprogrammed into iPSCs and characterized for alterations in metabolic parameters and the expression of marker genes indicating mitochondrial biogenesis. Fahd1-KO MEFs showed a higher reprogramming efficiency accompanied by a significant increase in glycolytic activity as compared to WT. We also observed a strong increase of mitochondrial DNA copy number and expression of biogenesis marker genes in Fahd1-KO iPSCs relative to WT. Neuronal differentiation of iPSCs was accompanied by increased expression of mitochondrial biogenesis genes in both WT and Fahd1-KO neurons with higher expression in Fahd1-KO neurons. Together these observations establish a role of FAHD1 as a potential negative regulator of reprogramming and add additional insight into mechanisms by which FAHD1 modulates mitochondrial functions.
- Subjects :
- Animals
Cell Differentiation
Cell Line
DNA, Mitochondrial metabolism
Fibroblasts cytology
Fibroblasts metabolism
Hydrolases deficiency
Induced Pluripotent Stem Cells cytology
Induced Pluripotent Stem Cells metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria genetics
Mitochondria metabolism
Neurons cytology
Neurons metabolism
Oxidative Phosphorylation
Cellular Reprogramming
Glycolysis physiology
Hydrolases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 10
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 34440809
- Full Text :
- https://doi.org/10.3390/cells10082040