@article{758c19805b2842448e96d65f3ed5c0db,
title = "Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity",
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.",
author = "A. Huyghe and G. Furlan and J. Schroeder and E. Cascales and A. Trajkova and M. Ruel and F. St{\"u}der and M. Larcombe and {Yang Sun}, {Y. Bo} and F. Mugnier and {De Matteo}, L. and A. Baygin and J. Wang and Y. Yu and N. Rama and B. Gibert and J. Kielbassa and L. Tonon and P. Wajda and N. Gadot and M. Brevet and M. Siouda and P. Mulligan and R. Dante and P. Liu and H. Gronemeyer and M. Mendoza-Parra and Polo, {J. M.} and F. Lavial",
note = "Funding Information: We are grateful to A. Lalande for technical assistance. We thank the Cancer Genomic Platform (Centre L{\'e}on B{\'e}rard, Cancer Research Center of Lyon) for performing the scRNA-Seq. This work was supported by institutional grants from INSERM/CNRS, ATIP-Avenir, Plan Cancer, Labex Dev2Can, Institut Convergence PLAsCAN (ANR-17-CONV-0002) and La Ligue Contre le Cancer Nationale et R{\'e}gionale (to F.L.), Institut National du Cancer (2019-L22 to F.L., M.M.-P., F.S. and H.G.), Fondation ARC (to F.L., G.F. and A.H.), Centre L{\'e}on B{\'e}rard (to F.L. and A.H.) and Fondation pour la Recherche M{\'e}dicale (to A.T.). P.M. and M.S. were funded by Institut National du Cancer (PLBIO2016-180) and Fondation pour la Recherche M{\'e}dicale (AJE20131128936). J.M.P was supported by an ARC Future Fellowship FT180100674 and NHMRC APP1104560. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = sep,
doi = "10.1038/s41556-022-00986-w",
language = "English",
volume = "24",
pages = "1350--1363",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "9",
}
