@article {924531,
	title = {Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.},
	journal = {Science},
	volume = {352},
	number = {6282},
	year = {2016},
	month = {2016 Apr 8},
	pages = {189-96},
	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.},
	keywords = {Base Sequence, Cell Communication, Cell Cycle, Drug Resistance, Neoplasm, Endothelial Cells, Genomics, Humans, Immunotherapy, Lymphocyte Activation, Melanoma, Microphthalmia-Associated Transcription Factor, Neoplasm Metastasis, RNA, Sequence Analysis, RNA, Single-Cell Analysis, Skin Neoplasms, Stromal Cells, T-Lymphocytes, Transcriptome, Tumor Microenvironment},
	issn = {1095-9203},
	doi = {10.1126/science.aad0501},
	author = {Itay Tirosh and Izar, Benjamin and Prakadan, Sanjay M and Wadsworth, Marc H and Treacy, Daniel and Trombetta, John J and Rotem, Asaf and Rodman, Christopher and Lian, Christine and Murphy, George and Fallahi-Sichani, Mohammad and Dutton-Regester, Ken and Lin, Jia-Ren and Cohen, Ofir and Shah, Parin and Lu, Diana and Genshaft, Alex S and Hughes, Travis K and Ziegler, Carly G K and Kazer, Samuel W and Gaillard, Aleth and Kolb, Kellie E and Villani, Alexandra-Chlo{\'e} and Johannessen, Cory M and Andreev, Aleksandr Y and Van Allen, Eliezer M and Bertagnolli, Monica and Sorger, Peter K and Sullivan, Ryan J and Flaherty, Keith T and Frederick, Dennie T and Jan{\'e}-Valbuena, Judit and Yoon, Charles H and Rozenblatt-Rosen, Orit and Shalek, Alex K and Regev, Aviv and Garraway, Levi A}
}
