Decoupling Genetics, Lineages, and Microenvironment in IDH-mutant Gliomas by Single-cell RNA-seq

Overview

Journal Science

Specialty Science

Date 2017 Apr 1

PMID 28360267

Citations 503

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 Suva

Affiliations

Soon will be listed here.

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.

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