RT Journal Article
SR Electronic
T1 In vivo reprogramming leads to premature death due to hepatic and intestinal failure
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.27.493700
DO 10.1101/2022.05.27.493700
A1 Parras, Alberto
A1 Vílchez-Acosta, Alba
A1 Desdín-Micó, Gabriela
A1 Mrabti, Calida
A1 Rechsteiner, Cheyenne
A1 Battiston, Fabrice
A1 Branchina, Clémence
A1 Pérez, Kevin
A1 Sempoux, Christine
A1 Ocampo, Alejandro
YR 2022
UL http://biorxiv.org/content/early/2022/05/27/2022.05.27.493700.abstract
AB SUMMARY The induction of cellular reprogramming by forced expression of the transcription factors OCT4, SOX2, KLF4, and C-MYC (OSKM) has been shown to allow the dedifferentiation of somatic cells and ameliorate age-associated phenotypes in multiple tissues and organs. Yet to date, the benefits of in vivo reprogramming are limited by the occurrence of detrimental side-effects. Here, using complementary genetic approaches, we demonstrated that continuous in vivo induction of the reprogramming factors leads to hepatic and intestinal dysfunction resulting in decreased body weight and premature death. By generating a novel transgenic reprogrammable mouse strain, which avoids OSKM expression in both liver and intestine, we drastically reduced the early lethality and adverse effects associated with in vivo reprogramming. This new reprogramming mouse allows safe and long-term continuous induction of OSKM and might enable a better understanding of in vivo reprogramming as well as maximize its potential effects on rejuvenation and regeneration.Competing Interest StatementThe authors have declared no competing interest.