Tissue damage and senescence provide critical signals for cellular reprogramming in vivo

Reprogramming of differentiated cells into pluripotent cells can occur in vivo, but the mechanisms involved remain to be elucidated. Senescence is a cellular response to damage, characterized by abundant production of cytokines and other secreted factors that, together with the recruitment of inflammatory cells, result in tissue remodeling. Here, we show that in vivo expression of the reprogramming factors OCT4, SOX2, KLF4, and cMYC (OSKM) in mice leads to senescence and reprogramming, both coexisting in close proximity. Genetic and pharmacological analyses indicate that OSKM-induced senescence requires the Ink4a/Arf locus and, through the production of the cytokine interleukin-6, creates a permissive tissue…

• FR
  Fundación Ramón Areces
• BS
  Banco Santander
• AR
  AXA Research Fund
• FB
  Fundación Botín
• ER
  European Regional Development Fund
• ES
  European Social Fund
• HE
  H2020 European Research Council