Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells

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• dc.contributor.author Ruiz, Sergioca
• dc.contributor.author Lopez Contreras, Andres J.ca
• dc.contributor.author Gabut, Mathieuca
• dc.contributor.author Marion, Rosa M.ca
• dc.contributor.author Gutiérrez Martínez, Paulaca
• dc.contributor.author Bua, Sabelaca
• dc.contributor.author Ramírez, Oscarca
• dc.contributor.author Olalde Marquínez, Íñigo, 1987-ca
• dc.contributor.author Rodrigo Perez, Saraca
• dc.contributor.author Li, Hanca
• dc.contributor.author Marquès i Bonet, Tomàs, 1975-ca
• dc.contributor.author Serrano, Manuelca
• dc.contributor.author Blasco, Maria A.ca
• dc.contributor.author Batada, Nizar N.ca
• dc.contributor.author Fernández Capetillo, Oscarca
• dc.date.accessioned 2016-01-27T16:37:08Z
• dc.date.available 2016-01-27T16:37:08Z
• dc.date.issued 2015
• dc.description.abstract The generation of induced pluripotent stem cells (iPSC) from adult somatic cells is one of the most remarkable discoveries in recent decades. However, several works have reported evidence of genomic instability in iPSC, raising concerns on their biomedical use. The reasons behind the genomic instability observed in iPSC remain mostly unknown. Here we show that, similar to the phenomenon of oncogene-induced replication stress, the expression of reprogramming factors induces replication stress. Increasing the levels of the checkpoint kinase 1 (CHK1) reduces reprogramming-induced replication stress and increases the efficiency of iPSC generation. Similarly, nucleoside supplementation during reprogramming reduces the load of DNA damage and genomic rearrangements on iPSC. Our data reveal that lowering replication stress during reprogramming, genetically or chemically, provides a simple strategy to reduce genomic instability on mouse and human iPSC.ca
• dc.description.sponsorship S.R. was funded by a Ramon y Cajal contract (RYC-2011-09242) and a grant (SAF2013-49147-P) from the MINECO. Work in NB laboratory was supported by a grant from the Ontario Institute for Cancer Research. T.M.-B. is supported by grants from the European Research Council (ERC StG 260372) and the Spanish Ministry of Economy and Competitiveness (BFU2011-28549). Work in O.F.-C. laboratory was supported by Fundación Botín, by Banco Santander through its Santander Universities Global Division and by grants from MINECO (SAF2011-23753), Worldwide Cancer Research (12-0229), Fundació La Marato de TV3, Howard Hughes Medical Institute and the European Research Council (ERC-617840).
• dc.format.mimetype application/pdfca
• dc.identifier.citation Ruiz S, Lopez-Contreras AJ, Gabut M, Marion RM, Gutierrez-Martinez P, Bua S et al. Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells. Nature Communications. 2015;6:8036. DOI: 10.1038/ncomms9036ca
• dc.identifier.doi http://dx.doi.org/10.1038/ncomms9036
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/25669
• dc.language.iso engca
• dc.publisher Nature Publishing Groupca
• dc.relation.ispartof Nature Communications. 2015;6:8036
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/260372
• dc.relation.projectID info:eu‐repo/grantAgreement/ES/3PN/BFU2011-28549
• dc.rights © Nature Publishing Group. http://dx.doi.org/10.1038/ncomms9036. This work is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
• dc.subject.other Biologia molecularca
• dc.subject.other Citologiaca
• dc.title Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cellsca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca