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 het...
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| Format: | Article |
| Language: | en_US |
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American Association for the Advancement of Science (AAAS)
2017
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| Online Access: | http://hdl.handle.net/1721.1/110559 https://orcid.org/0000-0002-5621-8768 https://orcid.org/0000-0001-9376-164X https://orcid.org/0000-0003-3079-5134 https://orcid.org/0000-0001-8291-8672 https://orcid.org/0000-0002-8279-7150 https://orcid.org/0000-0002-7380-9594 https://orcid.org/0000-0001-9179-7972 https://orcid.org/0000-0003-0710-7305 https://orcid.org/0000-0001-8567-2049 |
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| author | Tirosh, I. Izar, B. Treacy, D. Trombetta, J. J. Rotem, A. Rodman, C. Lian, C. Murphy, G. Fallahi-Sichani, M. Dutton-Regester, K. Lin, J.-R. Cohen, O. Shah, P. Lu, D. Villani, A.-C. Andreev, A. Y. Van Allen, E. M. Bertagnolli, M. Sorger, P. K. Sullivan, R. J. Flaherty, K. T. Frederick, D. T. Jane-Valbuena, J. Rozenblatt-Rosen, O. Prakadan, Sanjay Wadsworth, Marc Havens Genshaft, Alex S. Hughes, Travis K. Ziegler, Carly Kazer, Samuel Weisgurt Gaillard de Saint Germain, Alethe Kolb, Kellie Elizabeth Johannessen, Cory M. Yoon, Clifford H. Shalek, Alexander K Regev, Aviv Garraway, Levi A. |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Tirosh, I. Izar, B. Treacy, D. Trombetta, J. J. Rotem, A. Rodman, C. Lian, C. Murphy, G. Fallahi-Sichani, M. Dutton-Regester, K. Lin, J.-R. Cohen, O. Shah, P. Lu, D. Villani, A.-C. Andreev, A. Y. Van Allen, E. M. Bertagnolli, M. Sorger, P. K. Sullivan, R. J. Flaherty, K. T. Frederick, D. T. Jane-Valbuena, J. Rozenblatt-Rosen, O. Prakadan, Sanjay Wadsworth, Marc Havens Genshaft, Alex S. Hughes, Travis K. Ziegler, Carly Kazer, Samuel Weisgurt Gaillard de Saint Germain, Alethe Kolb, Kellie Elizabeth Johannessen, Cory M. Yoon, Clifford H. Shalek, Alexander K Regev, Aviv Garraway, Levi A. |
| author_sort | Tirosh, I. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:07:01Z |
| format | Article |
| id | mit-1721.1/110559 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:07:01Z |
| publishDate | 2017 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1105592022-10-01T08:18:28Z Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq Tirosh, I. Izar, B. Treacy, D. Trombetta, J. J. Rotem, A. Rodman, C. Lian, C. Murphy, G. Fallahi-Sichani, M. Dutton-Regester, K. Lin, J.-R. Cohen, O. Shah, P. Lu, D. Villani, A.-C. Andreev, A. Y. Van Allen, E. M. Bertagnolli, M. Sorger, P. K. Sullivan, R. J. Flaherty, K. T. Frederick, D. T. Jane-Valbuena, J. Rozenblatt-Rosen, O. Prakadan, Sanjay Wadsworth, Marc Havens Genshaft, Alex S. Hughes, Travis K. Ziegler, Carly Kazer, Samuel Weisgurt Gaillard de Saint Germain, Alethe Kolb, Kellie Elizabeth Johannessen, Cory M. Yoon, Clifford H. Shalek, Alexander K Regev, Aviv Garraway, Levi A. Massachusetts Institute of Technology. Institute for Medical Engineering & Science Broad Institute of MIT and Harvard Massachusetts Institute of Technology. Department of Chemistry Prakadan, Sanjay Wadsworth, Marc Havens Genshaft, Alex S. Hughes, Travis K. Ziegler, Carly Kazer, Samuel Weisgurt Gaillard de Saint Germain, Alethe Kolb, Kellie Elizabeth Johannessen, Cory M. Yoon, Clifford H. Shalek, Alexander K Regev, Aviv Garraway, Levi 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. National Cancer Institute (U.S.) (1U24CA180922) National Cancer Institute (U.S.) (P30-CA14051) 2017-07-07T19:22:03Z 2017-07-07T19:22:03Z 2016-04 2015-07 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/110559 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 https://orcid.org/0000-0002-5621-8768 https://orcid.org/0000-0001-9376-164X https://orcid.org/0000-0003-3079-5134 https://orcid.org/0000-0001-8291-8672 https://orcid.org/0000-0002-8279-7150 https://orcid.org/0000-0002-7380-9594 https://orcid.org/0000-0001-9179-7972 https://orcid.org/0000-0003-0710-7305 https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1126/science.aad0501 Science Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Tirosh, I. Izar, B. Treacy, D. Trombetta, J. J. Rotem, A. Rodman, C. Lian, C. Murphy, G. Fallahi-Sichani, M. Dutton-Regester, K. Lin, J.-R. Cohen, O. Shah, P. Lu, D. Villani, A.-C. Andreev, A. Y. Van Allen, E. M. Bertagnolli, M. Sorger, P. K. Sullivan, R. J. Flaherty, K. T. Frederick, D. T. Jane-Valbuena, J. Rozenblatt-Rosen, O. Prakadan, Sanjay Wadsworth, Marc Havens Genshaft, Alex S. Hughes, Travis K. Ziegler, Carly Kazer, Samuel Weisgurt Gaillard de Saint Germain, Alethe Kolb, Kellie Elizabeth Johannessen, Cory M. Yoon, Clifford H. Shalek, Alexander K Regev, Aviv Garraway, Levi A. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq |
| title | Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq |
| title_full | Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq |
| title_fullStr | Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq |
| title_full_unstemmed | Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq |
| title_short | Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq |
| title_sort | dissecting the multicellular ecosystem of metastatic melanoma by single cell rna seq |
| url | http://hdl.handle.net/1721.1/110559 https://orcid.org/0000-0002-5621-8768 https://orcid.org/0000-0001-9376-164X https://orcid.org/0000-0003-3079-5134 https://orcid.org/0000-0001-8291-8672 https://orcid.org/0000-0002-8279-7150 https://orcid.org/0000-0002-7380-9594 https://orcid.org/0000-0001-9179-7972 https://orcid.org/0000-0003-0710-7305 https://orcid.org/0000-0001-8567-2049 |
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