Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq

To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase. Single-cell analyses suggested distinct tumor microenvironmental patterns,…

• HH
  Howard Hughes Medical Institute
• HF
  Human Frontier Science Program
• MR
  Melanoma Research Alliance
• DM
  Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
• DC
  Dana-Farber Cancer Institute
• BI
  Broad Institute
• SS
  Searle Scholars Program
• NI
  National Institutes of Health

  Awards: DP2 OD020839, P50GM107618
• KC
  Klarman Cell Observatory, Broad Institute
• NC
  National Cancer Institute

  Awards: R35CA197737, K99CA194163, P30-CA14051, P01CA163222, 1U24CA180922