Mapping Lung Cancer Epithelial-Mesenchymal Transition States and Trajectories with Single-Cell Resolution

Loukia G. Karacosta, Benedict Anchang, Nikolaos Ignatiadis, Samuel C. Kimmey, Jalen A. Benson, Joseph B. Shrager, Robert Tibshirani, Sean C. Bendall, & Sylvia K. Plevritis

Mar 12, 2019

Received Date: 6th February 19

Elucidating a continuum of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in clinical samples promises new insights in cancer progression and drug response. Using mass cytometry time-course analysis, we resolve lung cancer EMT states through TGFβ-treatment and identify through TGFβ-withdrawal, an MET state previously unrealized.  We demonstrate significant differences between EMT and MET trajectories using a novel computational tool (TRACER) for reconstructing trajectories between cell states.  Additionally, we construct a lung cancer reference map of EMT and MET states referred to as the EMT-MET STAte MaP (STAMP). Using a neural net algorithm, we project clinical samples onto the EMT-MET STAMP to characterize their phenotypic profile with single-cell resolution in terms of our in vitro EMT-MET analysis. In summary, we provide a framework that can be extended to phenotypically characterize clinical samples in the context of in vitro studies showing differential EMT-MET traits related to metastasis and drug sensitivity.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature