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The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs

The generation of inducible pluripotent stem cells (iPSCs) is a revolutionary technique allowing production of pluripotent patient-specific cell lines used for disease modeling, drug screening, and cell therapy. Integrity of nuclear DNA (nDNA) is mandatory to allow iPSCs utilization, while quality c...

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Autores principales: Palombo, Flavia, Peron, Camille, Caporali, Leonardo, Iannielli, Angelo, Maresca, Alessandra, Di Meo, Ivano, Fiorini, Claudio, Segnali, Alice, Sciacca, Francesca L., Rizzo, Ambra, Levi, Sonia, Suomalainen, Anu, Prigione, Alessandro, Broccoli, Vania, Carelli, Valerio, Tiranti, Valeria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365099/
https://www.ncbi.nlm.nih.gov/pubmed/34329598
http://dx.doi.org/10.1016/j.stemcr.2021.06.016
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author Palombo, Flavia
Peron, Camille
Caporali, Leonardo
Iannielli, Angelo
Maresca, Alessandra
Di Meo, Ivano
Fiorini, Claudio
Segnali, Alice
Sciacca, Francesca L.
Rizzo, Ambra
Levi, Sonia
Suomalainen, Anu
Prigione, Alessandro
Broccoli, Vania
Carelli, Valerio
Tiranti, Valeria
author_facet Palombo, Flavia
Peron, Camille
Caporali, Leonardo
Iannielli, Angelo
Maresca, Alessandra
Di Meo, Ivano
Fiorini, Claudio
Segnali, Alice
Sciacca, Francesca L.
Rizzo, Ambra
Levi, Sonia
Suomalainen, Anu
Prigione, Alessandro
Broccoli, Vania
Carelli, Valerio
Tiranti, Valeria
author_sort Palombo, Flavia
collection PubMed
description The generation of inducible pluripotent stem cells (iPSCs) is a revolutionary technique allowing production of pluripotent patient-specific cell lines used for disease modeling, drug screening, and cell therapy. Integrity of nuclear DNA (nDNA) is mandatory to allow iPSCs utilization, while quality control of mitochondrial DNA (mtDNA) is rarely included in the iPSCs validation process. In this study, we performed mtDNA deep sequencing during the transition from parental fibroblasts to reprogrammed iPSC and to differentiated neuronal precursor cells (NPCs) obtained from controls and patients affected by mitochondrial disorders. At each step, mtDNA variants, including those potentially pathogenic, fluctuate between emerging and disappearing, and some having functional implications. We strongly recommend including mtDNA analysis as an unavoidable assay to obtain fully certified usable iPSCs and NPCs.
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spelling pubmed-83650992021-08-23 The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs Palombo, Flavia Peron, Camille Caporali, Leonardo Iannielli, Angelo Maresca, Alessandra Di Meo, Ivano Fiorini, Claudio Segnali, Alice Sciacca, Francesca L. Rizzo, Ambra Levi, Sonia Suomalainen, Anu Prigione, Alessandro Broccoli, Vania Carelli, Valerio Tiranti, Valeria Stem Cell Reports Article The generation of inducible pluripotent stem cells (iPSCs) is a revolutionary technique allowing production of pluripotent patient-specific cell lines used for disease modeling, drug screening, and cell therapy. Integrity of nuclear DNA (nDNA) is mandatory to allow iPSCs utilization, while quality control of mitochondrial DNA (mtDNA) is rarely included in the iPSCs validation process. In this study, we performed mtDNA deep sequencing during the transition from parental fibroblasts to reprogrammed iPSC and to differentiated neuronal precursor cells (NPCs) obtained from controls and patients affected by mitochondrial disorders. At each step, mtDNA variants, including those potentially pathogenic, fluctuate between emerging and disappearing, and some having functional implications. We strongly recommend including mtDNA analysis as an unavoidable assay to obtain fully certified usable iPSCs and NPCs. Elsevier 2021-07-29 /pmc/articles/PMC8365099/ /pubmed/34329598 http://dx.doi.org/10.1016/j.stemcr.2021.06.016 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Palombo, Flavia
Peron, Camille
Caporali, Leonardo
Iannielli, Angelo
Maresca, Alessandra
Di Meo, Ivano
Fiorini, Claudio
Segnali, Alice
Sciacca, Francesca L.
Rizzo, Ambra
Levi, Sonia
Suomalainen, Anu
Prigione, Alessandro
Broccoli, Vania
Carelli, Valerio
Tiranti, Valeria
The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs
title The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs
title_full The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs
title_fullStr The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs
title_full_unstemmed The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs
title_short The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs
title_sort relevance of mitochondrial dna variants fluctuation during reprogramming and neuronal differentiation of human ipscs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365099/
https://www.ncbi.nlm.nih.gov/pubmed/34329598
http://dx.doi.org/10.1016/j.stemcr.2021.06.016
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