دورية أكاديمية
Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity
| العنوان: | Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity |
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| المؤلفون: | Huyghe, A., Furlan, G., Schroeder, J., Cascales, E., Trajkova, A., Ruel, M., Stüder, F., Larcombe, M., Yang Sun, Y. Bo, Mugnier, F., de Matteo, L., Baygin, A., Wang, J., Yu, Y., Rama, N., Gibert, B., Kielbassa, J., Tonon, Laurie, Wajda, Pauline, Gadot, N., Brevet, M., Siouda, M., Mulligan, P., Dante, R., Liu, P., Gronemeyer, H., Mendoza-Parra, M., Polo, J., Lavial, Fabrice |
| المساهمون: | Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard Lyon, Monash University Clayton, Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage Evry (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), The Wellcome Trust Sanger Institute Cambridge, Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of South Australia Adelaide, ANR-17-CONV-0002,PLASCAN,Institut François Rabelais pour la recherche multidisciplinaire sur le cancer(2017) |
| المصدر: | ISSN: 1465-7392. |
| بيانات النشر: | HAL CCSD Nature Publishing Group |
| سنة النشر: | 2022 |
| المجموعة: | HAL-CEA (Commissariat à l'énergie atomique et aux énergies alternatives) |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-03852723; https://hal.science/hal-03852723Test; https://hal.science/hal-03852723/documentTest; https://hal.science/hal-03852723/file/s41556-022-00986-w.pdfTest |
| DOI: | 10.1038/s41556-022-00986-w |
| الإتاحة: | https://doi.org/10.1038/s41556-022-00986-wTest https://hal.science/hal-03852723Test https://hal.science/hal-03852723/documentTest https://hal.science/hal-03852723/file/s41556-022-00986-w.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.6C8806D4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41556-022-00986-w |
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