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© Research
Publication : Nature Communication

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature Communication - 01 Aug 2015

Ruiz S1, Lopez-Contreras AJ1, Gabut M2,3, Marion RM4, Gutierrez-Martinez P1, Bua S5, Ramirez O6, Olalde I6, Rodrigo-Perez S1, Li H5, Marques-Bonet T6,7, Serrano M8, Blasco MA4, Batada NN2,3, Fernandez-Capetillo O1.

Link to Pubmed [PMID] – 26292731

Nat Commun. 2015 Aug 21;6:8036

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.