2026-04-29T04:08:43Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/100032024-11-29T20:12:46Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Ruiz, Sergio author Lopez-Contreras, Andres J author Gabut, Mathieu author Marion, RM author Gutierrez-Martinez, Paula author Bua, Sabela author Ramirez, Oscar author Olalde, Iñigo author Rodrigo-Perez, Sara author Li, Han author Marques-Bonet, Tomas author Serrano, Manuel author Blasco, MA author Batada, Nizar N author Fernandez-Capetillo, Oscar author 2015-08-21 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. Nat Commun. 2015 Aug;6:8036. 2041-1723 http://hdl.handle.net/20.500.12105/10003 26292731 10.1038/ncomms9036 2041-1723 Nature communications Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells