TY - JOUR
T1 - Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq
AU - Venteicher, Andrew S.
AU - Tirosh, Itay
AU - Hebert, Christine
AU - Yizhak, Keren
AU - Neftel, Cyril
AU - Filbin, Mariella G.
AU - Hovestadt, Volker
AU - Escalante, Leah E.
AU - Shaw, McKenzie L.
AU - Rodman, Christopher
AU - Gillespie, Shawn M.
AU - Dionne, Danielle
AU - Luo, Christina C.
AU - Ravichandran, Hiranmayi
AU - Mylvaganam, Ravindra
AU - Mount, Christopher
AU - Onozato, Maristela L.
AU - Nahed, Brian V.
AU - Wakimoto, Hiroaki
AU - Curry, William T.
AU - Iafrate, A. John
AU - Rivera, Miguel N.
AU - Frosch, Matthew P.
AU - Golub, Todd R.
AU - Brastianos, Priscilla K.
AU - Getz, Gad
AU - Patel, Anoop P.
AU - Monje, Michelle
AU - Cahill, Daniel P.
AU - Rozenblatt-Rosen, Orit
AU - Louis, David N.
AU - Bernstein, Bradley E.
AU - Regev, Aviv
AU - Suvà, Mario L.
PY - 2017/3/31
Y1 - 2017/3/31
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85016574289&partnerID=8YFLogxK
U2 - 10.1126/science.aai8478
DO - 10.1126/science.aai8478
M3 - Article
C2 - 28360267
AN - SCOPUS:85016574289
SN - 0036-8075
VL - 355
JO - Science
JF - Science
IS - 6332
M1 - aai8478
ER -
