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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Sergio Ruiz, Andres J. Lopez-Contreras, Mathieu Gabut, Rosa M. Marion, Paula Gutierrez-Martinez, Sabela Bua, Oscar Ramirez, Iñigo Olalde, Sara Rodrigo-Perez, Han Li, Tomas Marques-Bonet, Manuel Serrano, Maria A. Blasco, Nizar N. Batada, Oscar Fernandez-Capetillo

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. More... »

PAGES

8036

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms9036

DOI

http://dx.doi.org/10.1038/ncomms9036

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042568626

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26292731


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