Organ‐Specific Dedifferentiation and Epigenetic Remodeling in In Vivo Reprogramming

ABSTRACT The advent of in vivo reprogramming through transient expression of the Yamanaka factors (OCT4, SOX2, KLF4, and c‐MYC) holds strong promise for regenerative medicine, despite ongoing concerns about safety and clinical applicability. This review synthesizes recent advances in in vivo reprogramming, focusing on its potential to restore regenerative competence and promote rejuvenation across diverse tissues, including the retina, skeletal muscle, heart, liver, brain, and intestine. We highlight mechanistic parallels and distinctions between injury‐induced dedifferentiation and OSKM‐mediated reprogramming, emphasizing the roles of dedifferentiation, transient regenerative progenitors, and epigenetic remodeling. Critical safety considerations—such as teratoma formation, organ failure, and loss of cell identity—are discussed alongside strategies designed to mitigate these risks, like cyclic induction and targeted delivery. Finally, we briefly note the growing translational interest in this field, alongside directing readers to recent reviews for detailed coverage of biotech initiatives. Collectively, this work underscores the transformative potential of in vivo reprogramming for both tissue regeneration and rejuvenation, while stressing the importance of precise spatiotemporal control for its safe clinical application.