Cellular plasticity in reprogramming, rejuvenation and tumorigenesis: a pioneer TF perspective.

Trends Cell Biol

Cellular Reprogramming, Stem Cells and Oncogenesis Laboratory, Equipe Labellisée la Ligue Contre le Cancer, Labex Dev2Can - Univeristy of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France. Electronic address:

Published: March 2024

AI Article Synopsis

  • The process of in vivo reprogramming using transcription factors Oct4, Sox2, Klf4, and c-Myc (OSKM) shows potential for rejuvenation and regeneration, but carries a risk of tumor development.
  • This review explores the transformative effects of in vivo reprogramming on aging and cellular regeneration, emphasizing the double-edged nature of cellular plasticity that can lead to both healing and cancer.
  • Understanding how to separate cellular identity, plasticity, and aging during reprogramming could help create safer rejuvenation and regenerative treatments without increasing tumor risks.

Article Abstract

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.

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http://dx.doi.org/10.1016/j.tcb.2023.07.013DOI Listing

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