Mapping lung cancer epithelial-mesenchymal transition states and trajectories with single-cell resolution

Nat Commun. 2019 Dec 6;10(1):5587. doi: 10.1038/s41467-019-13441-6.

Abstract

Elucidating the spectrum of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in clinical samples promises insights on cancer progression and drug resistance. Using mass cytometry time-course analysis, we resolve lung cancer EMT states through TGFβ-treatment and identify, through TGFβ-withdrawal, a distinct MET state. We demonstrate significant differences between EMT and MET trajectories using a computational tool (TRACER) for reconstructing trajectories between cell states. In addition, we construct a lung cancer reference map of EMT and MET states referred to as the EMT-MET PHENOtypic STAte MaP (PHENOSTAMP). Using a neural net algorithm, we project clinical samples onto the EMT-MET PHENOSTAMP to characterize their phenotypic profile with single-cell resolution in terms of our in vitro EMT-MET analysis. In summary, we provide a framework to phenotypically characterize clinical samples in the context of in vitro EMT-MET findings which could help assess clinical relevance of EMT in cancer in future studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cell Line, Tumor
  • Computational Biology
  • Cytophotometry / methods
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition / physiology*
  • Humans
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / pathology*
  • Phenotype
  • Systems Biology
  • Transforming Growth Factor beta / metabolism

Substances

  • Transforming Growth Factor beta