KLF4公司
重编程
体内
生物
SOX2
细胞生物学
体细胞
转录因子
遗传学
细胞
基因
作者
Alberto Parras,Alba Vílchez-Acosta,Gabriela Desdín-Micó,Sara Picó,Calida Mrabti,Elena Montenegro-Borbolla,Céline Yacoub Maroun,Amin Haghani,Robert T. Brooke,María del Carmen Maza,Cheyenne Rechsteiner,Fabrice Battiston,Clémence Branchina,Kevin Pérez,Steve Horvath,Claire Bertelli,Christine Sempoux,Alejandro Ocampo
出处
期刊:Nature Aging
日期:2023-11-27
卷期号:3 (12): 1509-1520
被引量:19
标识
DOI:10.1038/s43587-023-00528-5
摘要
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.
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