Open Access
Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq
Andrew S. Venteicher,Andrew S. Venteicher,Itay Tirosh,Christine Hebert,Christine Hebert,Keren Yizhak,Keren Yizhak,Cyril Neftel,Cyril Neftel,Cyril Neftel,Mariella G. Filbin,Mariella G. Filbin,Volker Hovestadt,Volker Hovestadt,Leah E. Escalante,Leah E. Escalante,McKenzie Shaw,McKenzie Shaw,Christopher Rodman,Shawn M. Gillespie,Danielle Dionne,Christina C. Luo,Hiranmayi Ravichandran,Ravindra Mylvaganam,Christopher Mount,Maristela L. Onozato,Brian V. Nahed,Hiroaki Wakimoto,William T. Curry,A. John Iafrate,Miguel Rivera,Miguel Rivera,Matthew P. Frosch,Todd R. Golub,Todd R. Golub,Todd R. Golub,Priscilla K. Brastianos,Gad Getz,Gad Getz,Anoop P. Patel,Michelle Monje,Daniel P. Cahill,Orit Rozenblatt-Rosen,David N. Louis,Bradley E. Bernstein,Bradley E. Bernstein,Aviv Regev,Aviv Regev,Aviv Regev,Mario L. Suvà,Mario L. Suvà +50 more
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In this article, the authors dissected the influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples.Abstract:
Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation. As tumor grade increases, we find enhanced proliferation of malignant cells, larger pools of undifferentiated glioma cells, and an increase in macrophage over microglia expression programs in TME. Our work provides a unifying model for IDH-mutant gliomas and a general framework for dissecting the differences among human tumor subclasses.read more
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The Immune Landscape of Cancer
Vesteinn Thorsson,David L Gibbs,Scott D. Brown,Denise M. Wolf,Dante S. Bortone,Tai-Hsien Ou Yang,Eduard Porta-Pardo,Galen F. Gao,Christopher L. Plaisier,James A. Eddy,Elad Ziv,Aedín C. Culhane,Evan O. Paull,I K Ashok Sivakumar,Andrew J. Gentles,Raunaq Malhotra,Farshad Farshidfar,Antonio Colaprico,Joel S. Parker,Lisle E. Mose,Nam S Vo,Jianfang Liu,Yuexin Liu,Janet S. Rader,Varsha Dhankani,Sheila Reynolds,Reanne Bowlby,Andrea Califano,Andrew D. Cherniack,Dimitris Anastassiou,Davide Bedognetti,Arvind Rao,Ken Chen,Alexander Krasnitz,Hai Hu,Tathiane M. Malta,Houtan Noushmehr,Houtan Noushmehr,Chandra Sekhar Pedamallu,Susan Bullman,Akinyemi I. Ojesina,Andrew Lamb,Wanding Zhou,Hui Shen,Toni K. Choueiri,John N. Weinstein,Justin Guinney,Joel H. Saltz,Robert A. Holt,Charles E Rabkin,Alexander J. Lazar +50 more
TL;DR: An extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA identifies six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis.
Journal ArticleDOI
Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer
Sidharth V. Puram,Itay Tirosh,Itay Tirosh,Anuraag S. Parikh,Anoop P. Patel,Keren Yizhak,Shawn M. Gillespie,Shawn M. Gillespie,Christopher Rodman,Christina L. Luo,Edmund A. Mroz,Kevin S. Emerick,Daniel G. Deschler,Daniel G. Deschler,Mark A. Varvares,Mark A. Varvares,Ravi Mylvaganam,Orit Rozenblatt-Rosen,James W. Rocco,James W. Rocco,James W. Rocco,William C. Faquin,Derrick T. Lin,Derrick T. Lin,Aviv Regev,Aviv Regev,Aviv Regev,Bradley E. Bernstein,Bradley E. Bernstein +28 more
TL;DR: In this article, the authors profiled transcriptomes of ∼6,000 single cells from 18 head and neck squamous cell carcinoma (HNSCC) patients, including five matched pairs of primary tumors and lymph node metastases.
Journal ArticleDOI
An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma
Cyril Neftel,Julie Laffy,Mariella G. Filbin,Toshiro Hara,Marni E. Shore,Marni E. Shore,Gilbert J. Rahme,Gilbert J. Rahme,Alyssa R. Richman,Alyssa R. Richman,Dana Silverbush,Dana Silverbush,McKenzie Shaw,Christine M. Hebert,Christine M. Hebert,John M. DeWitt,John M. DeWitt,Simon Gritsch,Simon Gritsch,Elizabeth M. Perez,Elizabeth M. Perez,L. Nicolas Gonzalez Castro,Xiaoyang Lan,Xiaoyang Lan,Nicholas Druck,Christopher Rodman,Danielle Dionne,Alexander Kaplan,Mia Bertalan,Julia L. Small,Kristine Pelton,Sarah Becker,Dennis M. Bonal,Quang-Dé Nguyen,Rachel L. Servis,Jeremy M. Fung,Ravindra Mylvaganam,Lisa Mayr,Johannes Gojo,Christine Haberler,René Geyeregger,Thomas Czech,Irene Slavc,Brian V. Nahed,William T. Curry,Bob S. Carter,Hiroaki Wakimoto,Priscilla K. Brastianos,Tracy T. Batchelor,Anat Stemmer-Rachamimov,Maria Martinez-Lage,Matthew P. Frosch,Ivan Stamenkovic,Nicolo Riggi,Esther Rheinbay,Esther Rheinbay,Michelle Monje,Orit Rozenblatt-Rosen,Daniel P. Cahill,Anoop P. Patel,Tony Hunter,Inder M. Verma,Keith L. Ligon,Keith L. Ligon,David N. Louis,Aviv Regev,Aviv Regev,Bradley E. Bernstein,Bradley E. Bernstein,Itay Tirosh,Mario L. Suvà,Mario L. Suvà +71 more
TL;DR: It is found that malignant cells in glioblastoma exist in four main cellular states that recapitulate distinct neural cell types, are influenced by the tumor microenvironment, and exhibit plasticity.
Journal ArticleDOI
Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding
Alexander B. Rosenberg,Charles M. Roco,Richard A. Muscat,Anna Kuchina,Paul J Sample,Zizhen Yao,Lucas T. Graybuck,David J. Peeler,Sumit Mukherjee,Wei Chen,Suzie H. Pun,Drew L. Sellers,Bosiljka Tasic,Georg Seelig +13 more
TL;DR: Split-pool ligation-based transcriptome sequencing (SPLiT-seq) as discussed by the authors is a single-cell RNA-seq method that labels the cellular origin of RNA through combinatorial barcoding.
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
TL;DR: 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.
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An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex
Ye Zhang,Kenian Chen,Steven A. Sloan,Mariko L. Bennett,Anja R. Scholze,Sean O'Keeffe,Hemali Phatnani,Paolo Guarnieri,Christine Caneda,Nadine Ruderisch,Shuyun Deng,Shane A. Liddelow,Chaolin Zhang,Richard Daneman,Tom Maniatis,Ben A. Barres,Jian Qian Wu +16 more
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Journal ArticleDOI
Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
Anoop P. Patel,Itay Tirosh,John J. Trombetta,Alex K. Shalek,Shawn M. Gillespie,Hiroaki Wakimoto,Daniel P. Cahill,Brian V. Nahed,William T. Curry,Robert L. Martuza,David N. Louis,Orit Rozenblatt-Rosen,Mario L. Suvà,Mario L. Suvà,Aviv Regev,Aviv Regev,Aviv Regev,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein +19 more
TL;DR: The genome sequence of single cells isolated from brain glioblastomas was examined, which revealed shared chromosomal changes but also extensive transcription variation, including genes related to signaling, which represent potential therapeutic targets.
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