Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq
Year: 2017
Type: article
Study design: Observational Study
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.
Source: Science
Authors: Andrew S. Venteicher, Itay Tirosh, Christine Hebert, Keren Yizhak, Cyril Neftel, Mariella G. Filbin, Volker Hovestadt, Leah E. Escalante, McKenzie L. 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 N. Rivera, Matthew P. Frosch, Todd R. Golub, Priscilla K. Brastianos, Gad Getz, Anoop P. Patel, Michelle Monje, Daniel P. Cahill, Orit Rozenblatt-Rosen, David N. Louis, Bradley E. Bernstein, Aviv Regev, Mario L. Suvà
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Howard Hughes Medical Institute, American Cancer Society, Richard and Susan Smith Family Foundation, V Foundation for Cancer Research, American Brain Tumor Association, Neurosurgery Research and Education Foundation, California Institute of Regenerative Medicine, Wellcome Trust, Broad Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, National Institutes of Health, Ludwig Center at Harvard, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Center for Research Resources
Awards: G1083602967, G1296697658, G1373451125, G1955872704, G2360436881, Translational Immunology Core's FACSAria Cell Sorter, G3197309817, G3934123819, G458629407, G4594333678, G4774430914, G5978557131, G6023769791, G6815014867, G6909165905, G863031104, G9000081591, G9000323787, Training Program in Nervous System Tumors, Cancer Center Support (Core) Grant, G941982536
OpenAlex ID: W2603523955