Self-sustaining long-term 3D epithelioid cultures reveal drivers of clonal expansion in esophageal epithelium.

Autor: Herms A; Wellcome Sanger Institute, Hinxton, UK.; Department of Biomedical Sciences, Universitat de Barcelona, Barcelona, Spain.; Lipid Trafficking and Disease Group, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain., Fernandez-Antoran D; Wellcome Sanger Institute, Hinxton, UK.; Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.; ARAID Foundation, Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain., Alcolea MP; Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK., Kalogeropoulou A; Wellcome Sanger Institute, Hinxton, UK., Banerjee U; Wellcome Sanger Institute, Hinxton, UK., Piedrafita G; Wellcome Sanger Institute, Hinxton, UK.; Department of Biochemistry and Molecular Biology, Complutense University of Madrid, Madrid, Spain.; Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Abby E; Wellcome Sanger Institute, Hinxton, UK., Valverde-Lopez JA; Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK., Ferreira IS; Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK., Caseda I; Department of Biomedical Sciences, Universitat de Barcelona, Barcelona, Spain.; Lipid Trafficking and Disease Group, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain., Bejar MT; Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK., Dentro SC; Wellcome Sanger Institute, Hinxton, UK.; European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK.; Artificial Intelligence in Oncology (B450), Deutsches Krebsforschungszentrum, Heidelberg, Germany., Vidal-Notari S; Department of Biochemistry and Molecular Biology, Complutense University of Madrid, Madrid, Spain.; Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Ong SH; Wellcome Sanger Institute, Hinxton, UK., Colom B; Wellcome Sanger Institute, Hinxton, UK.; Cambridge Institute of Science, Altos Labs, Cambridge, UK., Murai K; Wellcome Sanger Institute, Hinxton, UK., King C; Wellcome Sanger Institute, Hinxton, UK., Mahbubani K; Department of Surgery, University of Cambridge, Cambridge, UK.; Collaborative Biorepository for Translational Medicine (CBTM), Cambridge NIHR Biomedical Research Centre, Cambridge, UK., Saeb-Parsy K; Department of Surgery, University of Cambridge, Cambridge, UK.; Collaborative Biorepository for Translational Medicine (CBTM), Cambridge NIHR Biomedical Research Centre, Cambridge, UK., Lowe AR; Institute for Structural and Molecular Biology, University College London, London, UK.; Institute for the Physics of Living Systems, University College London, London, UK.; Department of Physics and Astronomy, University College London, London, UK., Gerstung M; European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK.; Artificial Intelligence in Oncology (B450), Deutsches Krebsforschungszentrum, Heidelberg, Germany., Jones PH; Wellcome Sanger Institute, Hinxton, UK. pj3@sanger.ac.uk.; Department of Oncology, Hutchison Research Centre, University of Cambridge, Cambridge, UK. pj3@sanger.ac.uk.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2024 Oct; Vol. 56 (10), pp. 2158-2173. Date of Electronic Publication: 2024 Sep 23.
DOI: 10.1038/s41588-024-01875-8
Abstrakt: Aging epithelia are colonized by somatic mutations, which are subjected to selection influenced by intrinsic and extrinsic factors. The lack of suitable culture systems has slowed the study of this and other long-term biological processes. Here, we describe epithelioids, a facile, cost-effective method of culturing multiple mouse and human epithelia. Esophageal epithelioids self-maintain without passaging for at least 1 year, maintaining a three-dimensional structure with proliferative basal cells that differentiate into suprabasal cells, which eventually shed and retain genomic stability. Live imaging over 5 months showed that epithelioids replicate in vivo cell dynamics. Epithelioids support genetic manipulation and enable the study of mutant cell competition and selection in three-dimensional epithelia, and show how anti-cancer treatments modulate competition between transformed and wild-type cells. Finally, a targeted CRISPR-Cas9 screen shows that epithelioids recapitulate mutant gene selection in aging human esophagus and identifies additional drivers of clonal expansion, resolving the genetic networks underpinning competitive fitness.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: