Linking the genotypes and phenotypes of cancer cells in heterogenous populations via real-time optical tagging and image analysis.

Autor: You L; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Su PR; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands.; Department of Chemistry, National Taiwan University, Taipei, Taiwan., Betjes M; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Rad RG; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Chou TC; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Beerens C; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van Oosten E; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Leufkens F; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Gasecka P; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands.; Department of Imaging Physics, Delft University of Technology, Delft, The Netherlands., Muraro M; Single Cell Discoveries, Utrecht, The Netherlands., van Tol R; Department of Imaging Physics, Delft University of Technology, Delft, The Netherlands., van Steenderen D; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Farooq S; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Hardillo JAU; Department of Otorhinolaryngology, Head and Neck Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands., de Jong RB; Department of Otorhinolaryngology, Head and Neck Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands., Brinks D; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands. d.brinks@tudelft.nl.; Department of Imaging Physics, Delft University of Technology, Delft, The Netherlands. d.brinks@tudelft.nl., Chien MP; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands. m.p.chien@erasmusmc.nl.; Erasmus MC Cancer Institute, Rotterdam, The Netherlands. m.p.chien@erasmusmc.nl.; Oncode Institute, Utrecht, The Netherlands. m.p.chien@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2022 May; Vol. 6 (5), pp. 667-675. Date of Electronic Publication: 2022 Mar 17.
DOI: 10.1038/s41551-022-00853-x
Abstrakt: Linking single-cell genomic or transcriptomic profiles to functional cellular characteristics, in particular time-varying phenotypic changes, could help unravel molecular mechanisms driving the growth of tumour-cell subpopulations. Here we show that a custom-built optical microscope with an ultrawide field of view, fast automated image analysis and a dye activatable by visible light enables the screening and selective photolabelling of cells of interest in large heterogeneous cell populations on the basis of specific functional cellular dynamics, such as fast migration, morphological variation, small-molecule uptake or cell division. Combining such functional single-cell selection with single-cell RNA sequencing allowed us to (1) functionally annotate the transcriptomic profiles of fast-migrating and spindle-shaped MCF10A cells, of fast-migrating MDA-MB-231 cells and of patient-derived head-and-neck squamous carcinoma cells, and (2) identify critical genes and pathways driving aggressive migration and mesenchymal-like morphology in these cells. Functional single-cell selection upstream of single-cell sequencing does not depend on molecular biomarkers, allows for the enrichment of sparse subpopulations of cells, and can facilitate the identification and understanding of the molecular mechanisms underlying functional phenotypes.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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