show Abstracthide AbstractWe combine extensive profiling of single-cell gene expression (scRNA-seq of 39,263 cells) and chromatin accessibility applied to ten genetically-homogeneous, patient-derived melanoma cultures, to examine intra- and intertumoral phenotypic heterogeneity, to identify new cell states, and to track dynamic transitions at single-cell resolution. Overall design: scRNA-seq (10x Genomics Chromium Single Cell 3' Solution V2 Chemistry and Drop-seq) of human melanoma cell lines with and without perturbations (SOX10-KD) Bulk RNA-seq of human melanoma cell lines with and without perturbations (baselines, SOX10/EGR3/NFATC2 knockdown and THZ2 treatment) ATAC-seq of human melanoma cell lines (untreated).