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High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts
- Source :
- Cells, Cells, Vol 10, Iss 2040, p 2040 (2021), Volume 10, Issue 8
- Publication Year :
- 2021
- Publisher :
- MDPI, 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 :
- Mice, Knockout
Neurons
QH301-705.5
Hydrolases
Induced Pluripotent Stem Cells
oxidative phosphorylation
reprogramming
iPSCs
Cell Differentiation
Fibroblasts
Cellular Reprogramming
DNA, Mitochondrial
Article
Cell Line
Mitochondria
Mice, Inbred C57BL
Mice
FAHD1
Animals
Biology (General)
neuronal differentiation
Glycolysis
glycolytic activity
Subjects
Details
- Language :
- English
- ISSN :
- 20734409
- Volume :
- 10
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.pmid.dedup....8f7785c79dfe9ffc69a5332a7682157f