CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem Cells

Stem Cell Reports. 2017 Feb 14;8(2):432-445. doi: 10.1016/j.stemcr.2016.12.009. Epub 2017 Jan 5.


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.

Keywords: DNA resection; cell reprogramming; genetic instability; iPSC.

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation / genetics
  • Cell Self Renewal / genetics
  • Cell Survival / genetics*
  • Cellular Reprogramming / genetics*
  • DNA Damage
  • Endodeoxyribonucleases
  • Genetic Fitness*
  • Genomic Instability
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism


  • Carrier Proteins
  • Cell Cycle Proteins
  • CtIP protein, mouse
  • Nuclear Proteins
  • Endodeoxyribonucleases
  • RBBP8 protein, human