Phenotypic heterogeneity and evolution of melanoma cells associated with targeted therapy resistance
Fig 5
Potential landscapes describing the drug-induced phenotypic evolution from melanocyte to mesenchymal phenotype for M397.
(A) The landscape of scalar potential extracted from the modified FP-type (Eq 3) kinetic model. The blue, cyan, and orange arrows indicate regions dominated by melanocytic (MART1+/NGFR±), neural-crest (MART1+/NFGR-) and mesenchymal (MART1-/NGFR-) phenotypes, respectively. (B) The free energy-like potential calculated by surprisal analysis shows the relative cell state stability with respect to the global steady state across different time points. The blue, cyan, and orange circles represent cell populations primarily at melanocytic, neural-crest and mesenchymal phenotypes at the respective time points. (C) Comparison between normalized free energy-like potential (from surprisal analysis, orange bar) and scalar potential (from modified FP-type kinetic model, blue bar) for D73, calculated from transcriptional profiles of unsorted and sorted NGFR-/MART-1- mesenchymal cells. (D) Cartoon illustration of the competition between state-dependent net growth and system stabilization towards the attractor state upon drug treatment.