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

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 rol...

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Autores principales: Salti, Ahmad, Etemad, Solmaz, Cubero, Marta Suarez, Albertini, Eva, Kovacs-Szalka, Beata, Holzknecht, Max, Cappuccio, Elia, Cavinato, Maria, Edenhofer, Frank, Jansen Dürr, Pidder
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392800/
https://www.ncbi.nlm.nih.gov/pubmed/34440809
http://dx.doi.org/10.3390/cells10082040
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author Salti, Ahmad
Etemad, Solmaz
Cubero, Marta Suarez
Albertini, Eva
Kovacs-Szalka, Beata
Holzknecht, Max
Cappuccio, Elia
Cavinato, Maria
Edenhofer, Frank
Jansen Dürr, Pidder
author_facet Salti, Ahmad
Etemad, Solmaz
Cubero, Marta Suarez
Albertini, Eva
Kovacs-Szalka, Beata
Holzknecht, Max
Cappuccio, Elia
Cavinato, Maria
Edenhofer, Frank
Jansen Dürr, Pidder
author_sort Salti, Ahmad
collection PubMed
description 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.
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spelling pubmed-83928002021-08-28 High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts Salti, Ahmad Etemad, Solmaz Cubero, Marta Suarez Albertini, Eva Kovacs-Szalka, Beata Holzknecht, Max Cappuccio, Elia Cavinato, Maria Edenhofer, Frank Jansen Dürr, Pidder Cells Article 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. MDPI 2021-08-10 /pmc/articles/PMC8392800/ /pubmed/34440809 http://dx.doi.org/10.3390/cells10082040 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Salti, Ahmad
Etemad, Solmaz
Cubero, Marta Suarez
Albertini, Eva
Kovacs-Szalka, Beata
Holzknecht, Max
Cappuccio, Elia
Cavinato, Maria
Edenhofer, Frank
Jansen Dürr, Pidder
High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts
title High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts
title_full High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts
title_fullStr High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts
title_full_unstemmed High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts
title_short High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts
title_sort high glycolytic activity enhances stem cell reprogramming of fahd1-ko mouse embryonic fibroblasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392800/
https://www.ncbi.nlm.nih.gov/pubmed/34440809
http://dx.doi.org/10.3390/cells10082040
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