Picó Sara, Vílchez-Acosta Alba, Agostinho de Sousa João, Maza María Del Carmen, Mrabti Calida, Parras Alberto, Desdín-Micó Gabriela, Maroun Céline Yacoub, Branchina Clémence, von Meyenn Ferdinand, Ocampo Alejandro
Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Laboratory of Nutrition and Metabolic Epigenetics, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
Cell Rep. 2025 Jul 22;44(7):115879. doi: 10.1016/j.celrep.2025.115879. Epub 2025 Jun 24.
In vivo reprogramming through the forced expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) has demonstrated great potential for reversing age-associated phenotypes. However, continuous in vivo OSKM expression has raised safety concerns due to loss of cell identity, decrease in body weight, and premature death. Although cyclic short-term or targeted expression of the reprogramming factors can mitigate some of these detrimental effects, systemic rejuvenation of wild-type mice has remained elusive. To improve the fundamental understanding of in vivo reprogramming, we conduct a comparative analysis of various reprogrammable mouse strains across multiple tissues and organs. In addition, we develop reprogrammable mouse strains by avoiding OSKM expression in specific organs or implementing expression approaches within specific cells, thereby offering safer strategies to induce in vivo reprogramming. We hope that these tools will become valuable resources for future research in this field of research with potential implications to human health.
通过强制表达Oct4、Sox2、Klf4和c-Myc（OSKM）进行体内重编程已显示出逆转与年龄相关表型的巨大潜力。然而，由于细胞身份丧失、体重减轻和过早死亡，体内持续表达OSKM引发了安全担忧。尽管重编程因子的周期性短期或靶向表达可以减轻其中一些有害影响，但野生型小鼠的全身年轻化仍然难以实现。为了增进对体内重编程的基本理解，我们对多种可重编程小鼠品系的多个组织和器官进行了比较分析。此外，我们通过避免在特定器官中表达OSKM或在特定细胞内实施表达方法来开发可重编程小鼠品系，从而提供更安全的策略来诱导体内重编程。我们希望这些工具将成为该研究领域未来研究的宝贵资源，对人类健康具有潜在意义。
