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Science DOI:10.1126/science.aai8478

Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq.

Publication TypeJournal Article
Year of Publication2017
AuthorsVenteicher, AS, Tirosh, I, Hebert, C, Yizhak, K, Neftel, C, Filbin, MG, Hovestadt, V, Escalante, LE, Shaw, MKL, Rodman, C, Gillespie, SM, Dionne, D, Luo, CC, Ravichandran, H, Mylvaganam, R, Mount, C, Onozato, ML, Nahed, BV, Wakimoto, H, Curry, WT, A Iafrate, J, Rivera, MN, Frosch, MP, Golub, TR, Brastianos, PK, Getz, G, Patel, AP, Monje, M, Cahill, DP, Rozenblatt-Rosen, O, Louis, DN, Bernstein, BE, Regev, A, Suvà, ML
Date Published2017 03 31
KeywordsBrain Neoplasms, Cell Lineage, Glioma, Humans, Isocitrate Dehydrogenase, Macrophages, Microglia, Neoplasm Grading, Neoplastic Stem Cells, Principal Component Analysis, Sequence Analysis, RNA, Single-Cell Analysis, Tumor Microenvironment

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.


Alternate JournalScience
PubMed ID28360267
PubMed Central IDPMC5519096
Grant ListR25 NS065743 / NS / NINDS NIH HHS / United States
U24 CA180922 / CA / NCI NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
K12 CA090354 / CA / NCI NIH HHS / United States
S10 RR023440 / RR / NCRR NIH HHS / United States
R33 CA202820 / CA / NCI NIH HHS / United States
/ / Wellcome Trust / United Kingdom
P50 CA165962 / CA / NCI NIH HHS / United States