Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity - CRCL-Reprogrammation cellulaire, cellules souches et oncogenèse Access content directly
Journal Articles Nature Cell Biology Year : 2022

Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity

F. Stüder
N. Rama
B. Gibert
M. Brevet
P. Liu
M. Mendoza-Parra

Abstract

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.
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Origin : Publication funded by an institution

Dates and versions

hal-03852723 , version 1 (15-11-2022)

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A. Huyghe, G. Furlan, J. Schroeder, E. Cascales, A. Trajkova, et al.. Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity. Nature Cell Biology, 2022, 24 (9), pp.1350-1363. ⟨10.1038/s41556-022-00986-w⟩. ⟨hal-03852723⟩
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