In vivo reprogramming leads to premature death linked to hepatic and intestinal failure.
Journal
Nature aging
ISSN: 2662-8465
Titre abrégé: Nat Aging
Pays: United States
ID NLM: 101773306
Informations de publication
Date de publication:
27 Nov 2023
27 Nov 2023
Historique:
received:
10
06
2022
accepted:
09
10
2023
medline:
28
11
2023
pubmed:
28
11
2023
entrez:
27
11
2023
Statut:
aheadofprint
Résumé
The induction of cellular reprogramming via expression of the transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM) can drive dedifferentiation of somatic cells and ameliorate age-associated phenotypes in multiple tissues and organs. However, the benefits of long-term in vivo reprogramming are limited by detrimental side-effects. Here, using complementary genetic approaches, we demonstrated that continuous induction of the reprogramming factors in vivo leads to hepatic and intestinal dysfunction resulting in decreased body weight and contributing to premature death (within 1 week). By generating a transgenic reprogrammable mouse strain, avoiding OSKM expression in both liver and intestine, we reduced the early lethality and adverse effects associated with in vivo reprogramming and induced a decrease in organismal biological age. This reprogramming mouse strain, which allows longer-term continuous induction of OSKM with attenuated toxicity, can help better understand rejuvenation, regeneration and toxicity during in vivo reprogramming.
Identifiants
pubmed: 38012287
doi: 10.1038/s43587-023-00528-5
pii: 10.1038/s43587-023-00528-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Molecular Biology Organization (EMBO)
ID : ALTF 444-2021
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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