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

Simple item page
dc.contributor.authorHuyghe, A.
dc.contributor.authorFurlan, G.
dc.contributor.authorSchroeder, J.
dc.contributor.authorCascales, E.
dc.contributor.authorTrajkova, A.
dc.contributor.authorRuel, M.
dc.contributor.authorStüder, F.
dc.contributor.authorLarcombe, M.
dc.contributor.authorYang Sun, Y.B.
dc.contributor.authorMugnier, F.
dc.contributor.authorDe Matteo, L.
dc.contributor.authorBaygin, A.
dc.contributor.authorWang, J.
dc.contributor.authorYu, Y.
dc.contributor.authorRama, N.
dc.contributor.authorGibert, B.
dc.contributor.authorKielbassa, J.
dc.contributor.authorTonon, L.
dc.contributor.authorWajda, P.
dc.contributor.authorGadot, N.
dc.contributor.authoret al.
dc.date.issued2022
dc.description.abstractCoordinated 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.
dc.description.statementofresponsibilityA. Huyghe ... J.M Polo ... et al.
dc.identifier.citationNature Cell Biology, 2022; 24(9):1350-1363
dc.identifier.doi10.1038/s41556-022-00986-w
dc.identifier.issn1465-7392
dc.identifier.issn1476-4679
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.urihttps://hdl.handle.net/2440/136650
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.granthttp://purl.org/au-research/grants/arc/FT180100674
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1104560
dc.rights© The Author(s) 2022 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/.
dc.source.urihttps://doi.org/10.1038/s41556-022-00986-w
dc.subjectTumor Suppressor Proteins
dc.subjectTranscription Factors
dc.subjectOctamer Transcription Factor-3
dc.subjectSOXB1 Transcription Factors
dc.subjectInduced Pluripotent Stem Cells
dc.subjectCellular Reprogramming
dc.subjectCell Plasticity
dc.subject.meshTumor Suppressor Proteins
dc.subject.meshTranscription Factors
dc.subject.meshOctamer Transcription Factor-3
dc.subject.meshSOXB1 Transcription Factors
dc.subject.meshInduced Pluripotent Stem Cells
dc.subject.meshCellular Reprogramming
dc.subject.meshCell Plasticity
dc.titleComparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Medicine publications
South Australian Immunogenomics Cancer Institute (SAIGENCI) publications