Open Access
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Itay Tirosh,Benjamin Izar,Daniel J. Treacy,John J. Trombetta,Asaf Rotem,Christopher Rodman,Christine G. Lian,George F. Murphy,Mohammad Fallahi-Sichani,Ken Dutton-Regester,Jia-Ren Lin,Ofir Cohen,Parin Shah,Diana Lu,Alexandra-Chloé Villani,Aleksandr Andreev,E.M. Van Allen,Monica M. Bertagnolli,Peter K. Sorger,Ryan J. Sullivan,Keith T. Flaherty,Dennie T. Frederick,Judit Jané-Valbuena,Orit Rozenblatt-Rosen,Sanjay M. Prakadan,Marc H. Wadsworth,Alex S. Genshaft,Travis K. Hughes,Carly G. K. Ziegler,Samuel W. Kazer,Alethe Gaillard de Saint Germain,Kellie E. Kolb,Cory M. Johannessen,Clifford H. Yoon,Alex K. Shalek,Aviv Regev,Levi A. Garraway +36 more
Reads0
Chats0
TLDR
Tirosh et al. as discussed by the authors applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells.Abstract:
Single-cell expression profiles of melanoma Tumors harbor multiple cell types that are thought to play a role in the development of resistance to drug treatments. Tirosh et al. used single-cell sequencing to investigate the distribution of these differing genetic profiles within melanomas. Many cells harbored heterogeneous genetic programs that reflected two different states of genetic expression, one of which was linked to resistance development. Following drug treatment, the resistance-linked expression state was found at a much higher level. Furthermore, the environment of the melanoma cells affected their gene expression programs. Science, this issue p. 189 Melanoma cells show transcriptional heterogeneity. 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.read more
Citations
More filters
Integrative analysis of 111 reference human epigenomes
Anshul Kundaje,Wouter Meuleman,Jason Ernst,Angela Yen,Pouya Kheradpour,Zhizhuo Zhang,Jianrong Wang,Lucas D. Ward,Abhishek Sarkar,Gerald Quon,Matthew L. Eaton,Yi-Chieh Wu,Andreas R. Pfenning,Xinchen Wang,Melina Claussnitzer,Yaping Liu,Mukul S. Bansal,Soheil Feizi-Khankandi,Ah Ram Kim,Richard C Sallari,Nicholas A Sinnott-Armstrong,Laurie A. Boyer,Elizabeta Gjoneska,Li-Huei Tsai,Manolis Kellis +24 more
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Revealing the vectors of cellular identity with single-cell genomics
TL;DR: Single-cell genomics has now made it possible to create a comprehensive atlas of human cells and has reopened definitions of a cell's identity and of the ways in which identity is regulated by the cell's molecular circuitry.
Journal ArticleDOI
The Tabula Sapiens: a multiple organ single cell transcriptomic atlas of humans
TL;DR: A human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor, enabled molecular characterization of more than 400 cell types, their distribution across tissues and tissue specific variation in gene expression.
Journal ArticleDOI
Decade-long leukaemia remissions with persistence of CD4+ CAR T cells
J. Joseph Melenhorst,Gregory M. Chen,Meng Wang,David L. Porter,Changya Chen,McKensie Collins,Peng Gao,Shovik Bandyopadhyay,Hongxing Sun,Ziran Zhao,Stefan Lundh,Iulian Pruteanu-Malinici,Christopher L. Nobles,Sayantan Maji,Noelle V. Frey,Saar Gill,Lifeng Tian,Irina Kulikovskaya,Minnal Gupta,David E Ambrose,Megan M. Davis,Joseph A. Fraietta,Jennifer Brogdon,Regina M. Young,Anne Chew,Bruce L. Levine,Don L. Siegel,Cécile Alanio,E. John Wherry,Frederic D. Bushman,Simon F. Lacey,Kai Tan,Carl H. June +32 more
TL;DR: In this article , the authors studied long-lasting CD19-redirected chimeric antigen receptor (CAR) T cells in two patients with chronic lymphocytic leukaemia who achieved a complete remission in 2010.
Journal ArticleDOI
Macrophages as tools and targets in cancer therapy
TL;DR: In this paper , the authors proposed a set of macrophage-targeting strategies that include inhibitors of cytokines and chemokines involved in the recruitment and polarization of tumour-promoting myeloid cells as well as activators of their antitumorigenic and immunostimulating functions.
References
More filters
Journal ArticleDOI
Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression
Li Yang,P. Charles Lin +1 more
TL;DR: This review summarizes recent progress, mechanistic understanding, and options for metastasis-targeted therapy.
Book ChapterDOI
Tim-3, Lag-3, and TIGIT.
Nicole Joller,Vijay K. Kuchroo +1 more
TL;DR: This work focuses on the co-inhibitory receptors Tim- 3, Lag-3, and TIGIT and how they regulate T cell function, maintenance of self-tolerance, their role in regulating ongoing T cell responses at peripheral tissues, and their synergistic effects in regulating autoimmunity and antitumor responses.
Journal ArticleDOI
Review of applications of high-throughput sequencing in personalized medicine: barriers and facilitators of future progress in research and clinical application
Gaye Lightbody,Valeriia Haberland,Fiona Browne,Laura E. Taggart,Huiru Zheng,Eileen Parkes,Jaine K. Blayney +6 more
TL;DR: An up-to-date overview of the evolution of HTS and the accompanying tools, infrastructure and data management approaches that are emerging in this space, which, if used within in a multidisciplinary context, may ultimately facilitate the development of personalized medicine.
Journal ArticleDOI
Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma.
Lan Hoang-Minh,Florian A. Siebzehnrubl,Changlin Yang,Silveli Suzuki-Hatano,Kyle Dajac,Tyler Loche,Nicholas Andrews,Michael Schmoll Massari,Jaimin S. Patel,Krisha Amin,Alvin Vuong,Ana Jimenez-Pascual,Paul Kubilis,Timothy J. Garrett,Craig G. Moneypenny,Christina A. Pacak,Jianping Huang,Elias Sayour,Duane Mitchell,Matthew R. Sarkisian,Brent A. Reynolds,Loic P. Deleyrolle +21 more
TL;DR: The studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABp7‐related metabolic pathways is a viable therapeutic strategy.
Journal ArticleDOI
Dynamic interplay between tumour, stroma and immune system can drive or prevent tumour progression
R J Seager,Cynthia Hajal,Fabian Spill,Fabian Spill,Roger D. Kamm,Muhammad H. Zaman,Muhammad H. Zaman +6 more
TL;DR: A comprehensive understanding of cancer in the context of dynamical interactions of the immune system and the tumour stroma is required to truly understand the progression toward and past malignancy.
Related Papers (5)
Abstract 4380: Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-sequencing
Benjamin Izar,Itay Tirsh,Sanjay Prakadan,Marc Wadsworth,Daniel J. Treacy,John J. Trombetta,Asaf Rotem,Christine G. Lian,George F. Murphy,Mohammad Fallahi-Sichani,Ken Dutton-Regester,Jia-Ren Lin,Judit Jané-Valbuena,Orit Rozenblatt-Rosen,Charles H. Yoon,Alex K. Shalek,Aviv Regev,Levi A. Garraway +17 more
Understanding tumor-infiltrating lymphocytes by single cell RNA sequencing.
Xianwen Ren,Zemin Zhang +1 more