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

• DOI: 10.1126/science.aai8478
• Publication Date: 2017-03-30T18:08:20Z
• 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 Ravicha...; 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. Bras...; Gad Getz; Anoop P. Patel; Michelle Monje; Daniel P. Cahill; Orit Rozenblatt-R...; David N. Louis; Bradley E. Bernstein; Aviv Regev; Mario L. Suvà
• Keywords: Isocitrate dehydrogenase

Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well composition 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 165 samples. Differences between IDH-mutant astrocytoma oligodendroglioma can be primarily explained distinct TME signature genetic events, whereas both types share similar developmental hierarchies lineages glial differentiation. As grade increases, we find enhanced proliferation cells, larger pools undifferentiated glioma an increase macrophage over microglia expression programs TME. Our work provides a unifying model for general framework dissecting differences among human subclasses.