RT Journal Article
T1 CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem Cells.
A1 Gómez-Cabello, Daniel
A1 Checa-Rodríguez, Cintia
A1 Abad, María
A1 Serrano, Manuel
A1 Huertas, Pablo
K1 DNA resection
K1 cell reprogramming
K1 genetic instability
K1 iPSC
AB 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.
YR 2017
FD 2017-01-05
LK http://hdl.handle.net/10668/10755
UL http://hdl.handle.net/10668/10755
LA en
DS RISalud
RD Apr 19, 2025