Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity
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...
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| Veröffentlicht in: | Nature cell biology 2022-09, Vol.24 (9), p.1350-1363 |
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| creator | 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, L. Wajda, P. Gadot, N. Brevet, M. Siouda, M. Mulligan, P. Dante, R. Liu, P. Gronemeyer, H. Mendoza-Parra, M. Polo, J. M. Lavial, F. |
| description | 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.
Huyghe, Furlan et al. compare pluripotent reprogramming with oncogenic transformation and identify Bcl11b and Atoh8 as regulators of cellular plasticity in both processes, thus offering a unifying theory on the factors constraining cell fate changes. |
| doi_str_mv | 10.1038/s41556-022-00986-w |
| format | Article |
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M.</creatorcontrib><creatorcontrib>Lavial, F.</creatorcontrib><title>Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>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. 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M.</creatorcontrib><creatorcontrib>Lavial, F.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huyghe, A.</au><au>Furlan, G.</au><au>Schroeder, J.</au><au>Cascales, E.</au><au>Trajkova, A.</au><au>Ruel, M.</au><au>Stüder, F.</au><au>Larcombe, M.</au><au>Yang Sun, Y. Bo</au><au>Mugnier, F.</au><au>De Matteo, L.</au><au>Baygin, A.</au><au>Wang, J.</au><au>Yu, Y.</au><au>Rama, N.</au><au>Gibert, B.</au><au>Kielbassa, J.</au><au>Tonon, L.</au><au>Wajda, P.</au><au>Gadot, N.</au><au>Brevet, M.</au><au>Siouda, M.</au><au>Mulligan, P.</au><au>Dante, R.</au><au>Liu, P.</au><au>Gronemeyer, H.</au><au>Mendoza-Parra, M.</au><au>Polo, J. M.</au><au>Lavial, F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2022-09-01</date><risdate>2022</risdate><volume>24</volume><issue>9</issue><spage>1350</spage><epage>1363</epage><pages>1350-1363</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><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.
Huyghe, Furlan et al. compare pluripotent reprogramming with oncogenic transformation and identify Bcl11b and Atoh8 as regulators of cellular plasticity in both processes, thus offering a unifying theory on the factors constraining cell fate changes.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>36075976</pmid><doi>10.1038/s41556-022-00986-w</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-2531-778X</orcidid><orcidid>https://orcid.org/0000-0003-1614-7755</orcidid><orcidid>https://orcid.org/0000-0002-5295-3124</orcidid><orcidid>https://orcid.org/0000-0002-1450-925X</orcidid><orcidid>https://orcid.org/0000-0001-9752-4393</orcidid><orcidid>https://orcid.org/0000-0001-5774-9678</orcidid><orcidid>https://orcid.org/0000-0003-2275-691X</orcidid><orcidid>https://orcid.org/0000-0003-4642-9999</orcidid><orcidid>https://orcid.org/0000-0001-9454-2449</orcidid><orcidid>https://orcid.org/0000-0003-1198-4925</orcidid><orcidid>https://orcid.org/0000-0003-3549-3960</orcidid><orcidid>https://orcid.org/0000-0002-1809-1727</orcidid><orcidid>https://orcid.org/0009-0005-8794-7276</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-7392 |
| ispartof | Nature cell biology, 2022-09, Vol.24 (9), p.1350-1363 |
| issn | 1465-7392 1476-4679 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9481462 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | 38 631/532/2128 631/532/2435 631/67/395 Biology Biomedical and Life Sciences c-Myc protein Cancer Cancer Research Cell Biology Cell fate Cell Plasticity - genetics Cellular Reprogramming - genetics Developmental Biology Frizzled-related protein 1 Gene expression Induced Pluripotent Stem Cells - metabolism Intermediates KLF4 protein Laboratories Life Sciences Medical research Myc protein Oct-4 protein Octamer Transcription Factor-3 - genetics Plastic foam Plastic properties Plasticity Pluripotency Research centers SOXB1 Transcription Factors - genetics Stem Cells Transcription factors Transcription Factors - metabolism Transformations Tumor Suppressor Proteins - metabolism |
| title | Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T12%3A53%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Comparative%20roadmaps%20of%20reprogramming%20and%20oncogenic%20transformation%20identify%20Bcl11b%20and%20Atoh8%20as%20broad%20regulators%20of%20cellular%20plasticity&rft.jtitle=Nature%20cell%20biology&rft.au=Huyghe,%20A.&rft.date=2022-09-01&rft.volume=24&rft.issue=9&rft.spage=1350&rft.epage=1363&rft.pages=1350-1363&rft.issn=1465-7392&rft.eissn=1476-4679&rft_id=info:doi/10.1038/s41556-022-00986-w&rft_dat=%3Cproquest_pubme%3E2712845700%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2715006762&rft_id=info:pmid/36075976&rfr_iscdi=true |