Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
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Shalek_Dissecting the.pdf
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Author(s)
Tirosh, I.
Izar, B.
Treacy, D.
Trombetta, J. J.
Rotem, A.
Rodman, C.
Lian, C.
Murphy, G.
Fallahi-Sichani, M.
Dutton-Regester, K.
Date Issued
April 2016
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Tirosh, I.; Izar, B.; Prakadan, S. M.; Wadsworth, M. H.; Treacy, D.; Trombetta, J. J.; Rotem, A.; Rodman, C.; Lian, C. et al. "Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq." Science 352, 6282 (April 2016): 189-196 © 2016 American Association for the Advancement of Science
Version
Author's final manuscript
Abstract
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, including cell-to-cell interactions. Analysis of tumor-infiltrating T cells revealed exhaustion programs, their connection to T cell activation and clonal expansion, and their variability across patients. Overall, we begin to unravel the cellular ecosystem of tumors and how single-cell genomics offers insights with implications for both targeted and immune therapies.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1126/science.aad0501
