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Open Access Publications from the University of California

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

  • Author(s): Karacosta, Loukia G
  • Anchang, Benedict
  • Ignatiadis, Nikolaos
  • Kimmey, Samuel C
  • Benson, Jalen A
  • Shrager, Joseph B
  • Tibshirani, Robert
  • Bendall, Sean C
  • Plevritis, Sylvia K
  • et al.
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.

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