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Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.
Tirosh, Itay; Izar, Benjamin; Prakadan, Sanjay M; Wadsworth, Marc H; Treacy, Daniel; Trombetta, John J; Rotem, Asaf; Rodman, Christopher; Lian, Christine; Murphy, George; Fallahi-Sichani, Mohammad; Dutton-Regester, Ken; Lin, Jia-Ren; Cohen, Ofir; Shah, Parin; Lu, Diana; Genshaft, Alex S; Hughes, Travis K; Ziegler, Carly G K; Kazer, Samuel W; Gaillard, Aleth; Kolb, Kellie E; Villani, Alexandra-Chloé; Johannessen, Cory M; Andreev, Aleksandr Y; Van Allen, Eliezer M; Bertagnolli, Monica; Sorger, Peter K; Sullivan, Ryan J; Flaherty, Keith T; Frederick, Dennie T; Jané-Valbuena, Judit; Yoon, Charles H; Rozenblatt-Rosen, Orit; Shalek, Alex K; Regev, Aviv; Garraway, Levi A.
Afiliação
  • Tirosh I; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Izar B; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA. bizar@partners.org aregev@broadinstitu
  • Prakadan SM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02142, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harva
  • Wadsworth MH; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02142, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harva
  • Treacy D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Trombetta JJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Rotem A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Rodman C; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lian C; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Murphy G; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Fallahi-Sichani M; Program in Therapeutic Sciences, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
  • Dutton-Regester K; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Lin JR; HMS LINCS Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • Cohen O; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Shah P; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
  • Lu D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Genshaft AS; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02142, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harva
  • Hughes TK; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, Cambridge, MA 02139, USA. Division of Hea
  • Ziegler CG; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, Cambridge, MA 02139, USA. Division of Hea
  • Kazer SW; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02142, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harva
  • Gaillard A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02142, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harva
  • Kolb KE; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02142, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harva
  • Villani AC; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Johannessen CM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Andreev AY; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Van Allen EM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Bertagnolli M; Department of Surgical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Department of Surgical Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Sorger PK; Program in Therapeutic Sciences, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. HMS LINCS Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Ludwig Center at Harvard, Boston, MA 02215, USA.
  • Sullivan RJ; Division of Medical Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
  • Flaherty KT; Division of Medical Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
  • Frederick DT; Division of Medical Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
  • Jané-Valbuena J; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Yoon CH; Department of Surgical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Department of Surgical Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Rozenblatt-Rosen O; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Shalek AK; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02142, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harva
  • Regev A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Biology and Koch Institute, MIT, Boston, MA 02142, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. bizar@partners.org aregev@broadinstitute.org levi_garraway@dfci.harvard.edu.
  • Garraway LA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. bizar@partners.org aregev@broadinstitute.org levi_garraway@dfci.harvard.edu.
Science ; 352(6282): 189-96, 2016 Apr 08.
Article em En | MEDLINE | ID: mdl-27124452
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Microambiente Tumoral / Melanoma Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Microambiente Tumoral / Melanoma Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article