通过转录因子（TFs）Oct4，Sox2，Klf4和c-Myc（OSKM）介导的体内重编程的多步骤过程，为重振和再生策略的发展带来了巨大的希望。然而，迄今为止开发的大部分方法都伴随着持续的肿瘤发生风险。在本文中，我们重点回顾了体内重编程的开创性效果，特别关注其对重振和再生的作用。我们讨论了先驱性转录因子活性如何产生细胞可塑性，这可能对诱导重编程、再生以及癌症的发生都至关重要。最后，我们强调在重编程过程中解耦细胞身份、可塑性和衰老的更好理解，可能为无肿瘤发生的重振/再生策略的开发铺平道路。 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

The multistep process of in vivo reprogramming, mediated by the transcription factors (TFs) Oct4, Sox2, Klf4, and c-Myc (OSKM), holds great promise for the development of rejuvenating and regenerative strategies. However, most of the approaches developed so far are accompanied by a persistent risk of tumorigenicity. Here, we review the groundbreaking effects of in vivo reprogramming with a particular focus on rejuvenation and regeneration. We discuss how the activity of pioneer TFs generates cellular plasticity that may be critical for inducing not only reprogramming and regeneration, but also cancer initiation. Finally, we highlight how a better understanding of the uncoupled control of cellular identity, plasticity, and aging during reprogramming might pave the way to the development of rejuvenating/regenerating strategies in a nontumorigenic manner.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.