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Cells
Volume 10
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10.3390/cells10082040
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Article

High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts

by
Ahmad Salti
1,2,*,†,
Solmaz Etemad
3,†,
Marta Suarez Cubero
1,
Eva Albertini
3,
Beata Kovacs-Szalka
3,
Max Holzknecht
3,
Elia Cappuccio
3,
Maria Cavinato
3,
Frank Edenhofer
1 and
Pidder Jansen Dürr
3,*
1
Institute of Molecular Biology and CMBI, Department of Genomics, Stem Cell Biology and Regenerative Medicine, University of Innsbruck, 6020 Innsbruck, Austria
2
Center for Medical Research, University Clinic for Ophthalmology and Optometry, Johannes Kepler University Linz, 4020 Linz, Austria
3
Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria
*
Authors to whom correspondence should be addressed.
†
Equally contributed.
Cells 2021, 10(8), 2040; https://doi.org/10.3390/cells10082040
Submission received: 5 July 2021 / Revised: 4 August 2021 / Accepted: 6 August 2021 / Published: 10 August 2021
(This article belongs to the Section Stem Cells)
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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.
Keywords: FAHD1; reprogramming; iPSCs; mitochondria; glycolytic activity; oxidative phosphorylation; neuronal differentiation FAHD1; reprogramming; iPSCs; mitochondria; glycolytic activity; oxidative phosphorylation; neuronal differentiation
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MDPI and ACS Style

Salti, A.; Etemad, S.; Cubero, M.S.; Albertini, E.; Kovacs-Szalka, B.; Holzknecht, M.; Cappuccio, E.; Cavinato, M.; Edenhofer, F.; Jansen Dürr, P. High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts. Cells 2021, 10, 2040. https://doi.org/10.3390/cells10082040

AMA Style

Salti A, Etemad S, Cubero MS, Albertini E, Kovacs-Szalka B, Holzknecht M, Cappuccio E, Cavinato M, Edenhofer F, Jansen Dürr P. High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts. Cells. 2021; 10(8):2040. https://doi.org/10.3390/cells10082040

Chicago/Turabian Style

Salti, Ahmad, Solmaz Etemad, Marta Suarez Cubero, Eva Albertini, Beata Kovacs-Szalka, Max Holzknecht, Elia Cappuccio, Maria Cavinato, Frank Edenhofer, and Pidder Jansen Dürr. 2021. "High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts" Cells 10, no. 8: 2040. https://doi.org/10.3390/cells10082040

APA Style

Salti, A., Etemad, S., Cubero, M. S., Albertini, E., Kovacs-Szalka, B., Holzknecht, M., Cappuccio, E., Cavinato, M., Edenhofer, F., & Jansen Dürr, P. (2021). High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts. Cells, 10(8), 2040. https://doi.org/10.3390/cells10082040

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