CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem Cells
Acquired genomic instability is one of the major concerns for the clinical use of induced pluripotent stem cells (iPSCs). All reprogramming methods are accompanied by the induction of DNA damage, of which double-strand breaks are the most cytotoxic and mutagenic. Consequently, DNA repair genes seem...
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doaj-19d4302e80e6462e855046174e580fb52020-11-24T22:45:12ZengElsevierStem Cell Reports2213-67112017-02-018243244510.1016/j.stemcr.2016.12.009CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem CellsDaniel Gómez-Cabello0Cintia Checa-Rodríguez1María Abad2Manuel Serrano3Pablo Huertas4Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Seville 41092, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Seville 41092, SpainTumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, SpainTumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Seville 41092, SpainAcquired genomic instability is one of the major concerns for the clinical use of induced pluripotent stem cells (iPSCs). All reprogramming methods are accompanied by the induction of DNA damage, of which double-strand breaks are the most cytotoxic and mutagenic. Consequently, DNA repair genes seem to be relevant for accurate reprogramming to minimize the impact of such DNA damage. Here, we reveal that reprogramming is associated with high levels of DNA end resection, a critical step in homologous recombination. Moreover, the resection factor CtIP is essential for cell reprogramming and establishment of iPSCs, probably to repair reprogramming-induced DNA damage. Our data reveal a new role for DNA end resection in maintaining genomic stability during cell reprogramming, allowing DNA repair fidelity to be retained in both human and mouse iPSCs. Moreover, we demonstrate that reprogramming in a resection-defective environment has long-term consequences on stem cell self-renewal and differentiation.http://www.sciencedirect.com/science/article/pii/S2213671116302995iPSCcell reprogramminggenetic instabilityDNA resection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daniel Gómez-Cabello Cintia Checa-Rodríguez María Abad Manuel Serrano Pablo Huertas |
spellingShingle |
Daniel Gómez-Cabello Cintia Checa-Rodríguez María Abad Manuel Serrano Pablo Huertas CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem Cells Stem Cell Reports iPSC cell reprogramming genetic instability DNA resection |
author_facet |
Daniel Gómez-Cabello Cintia Checa-Rodríguez María Abad Manuel Serrano Pablo Huertas |
author_sort |
Daniel Gómez-Cabello |
title |
CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem Cells |
title_short |
CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem Cells |
title_full |
CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem Cells |
title_fullStr |
CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem Cells |
title_full_unstemmed |
CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem Cells |
title_sort |
ctip-specific roles during cell reprogramming have long-term consequences in the survival and fitness of induced pluripotent stem cells |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2017-02-01 |
description |
Acquired genomic instability is one of the major concerns for the clinical use of induced pluripotent stem cells (iPSCs). All reprogramming methods are accompanied by the induction of DNA damage, of which double-strand breaks are the most cytotoxic and mutagenic. Consequently, DNA repair genes seem to be relevant for accurate reprogramming to minimize the impact of such DNA damage. Here, we reveal that reprogramming is associated with high levels of DNA end resection, a critical step in homologous recombination. Moreover, the resection factor CtIP is essential for cell reprogramming and establishment of iPSCs, probably to repair reprogramming-induced DNA damage. Our data reveal a new role for DNA end resection in maintaining genomic stability during cell reprogramming, allowing DNA repair fidelity to be retained in both human and mouse iPSCs. Moreover, we demonstrate that reprogramming in a resection-defective environment has long-term consequences on stem cell self-renewal and differentiation. |
topic |
iPSC cell reprogramming genetic instability DNA resection |
url |
http://www.sciencedirect.com/science/article/pii/S2213671116302995 |
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