Transcriptional and chromatin accessibility profiling of melanoma cells during BRAF inhibitor–induced drug tolerance

Drug tolerance can emerge rapidly in melanoma following treatment with BRAF inhibitors. This transition has been associated with transcriptional and chromatin state remodeling. To investigate the molecular features of this process, we profiled melanoma cells before and during exposure to a BRAF inhibitor. We generated single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing (bulk RNA-seq), and bulk ATAC-seq datasets from SKMEL5 melanoma cells. Cells were analyzed under untreated conditions and following treatment with 8 µM BRAF inhibitor (PLX4720) for defined time periods corresponding to drug-tolerant states. Bulk RNA-seq was performed on multiple SKMEL5 subclones (SC01, SC07, SC10) to characterize transcriptional responses across biological replicates. scRNA-seq and ATAC-seq were used to profile transcriptional heterogeneity and chromatin accessibility changes associated with drug tolerance.