Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity.
Fiche publication
Date publication
septembre 2022
Journal
Nature cell biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRONEMEYER Hinrich
Tous les auteurs :
Huyghe A, Furlan G, Schroeder J, Cascales E, Trajkova A, Ruel M, Stüder F, Larcombe M, Yang Sun YB, Mugnier F, De Matteo L, Baygin A, Wang J, Yu Y, Rama N, Gibert B, Kielbassa J, Tonon L, Wajda P, Gadot N, Brevet M, Siouda M, Mulligan P, Dante R, Liu P, Gronemeyer H, Mendoza-Parra M, Polo JM, Lavial F
Lien Pubmed
Résumé
Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.
Référence
Nat Cell Biol. 2022 09 8;: