Single-cell analysis resolves the cell state transition and signaling dynamics associated with melanoma drug-induced resistance.

ABSTRACT: Continuous BRAF inhibition of BRAF mutant melanomas triggers a series of cell state changes that lead to therapy resistance and escape from immune control before establishing acquired resistance genetically. We used genome-wide transcriptomics and single-cell phenotyping to explore the response kinetics to BRAF inhibition for a panel of patient-derived BRAF^V600 -mutant melanoma cell lines. A subset of plastic cell lines, which followed a trajectory covering multiple known cell state transitions, provided models for more detailed biophysical investigations. Markov modeling revealed that the cell state transitions were reversible and mediated by both Lamarckian induction and nongenetic Darwinian selection of drug-tolerant states. Single-cell functional proteom

SUBMITTER: Su Y 

PROVIDER: S-EPMC5748184 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature