Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma.

Science
Authors
Keywords
Abstract

Human cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes, and epigenetic states, but current models do not adequately reflect tumor composition in patients. We used single-cell RNA sequencing (RNA-seq) to profile 430 cells from five primary glioblastomas, which we found to be inherently variable in their expression of diverse transcriptional programs related to oncogenic signaling, proliferation, complement/immune response, and hypoxia. We also observed a continuum of stemness-related expression states that enabled us to identify putative regulators of stemness in vivo. Finally, we show that established glioblastoma subtype classifiers are variably expressed across individual cells within a tumor and demonstrate the potential prognostic implications of such intratumoral heterogeneity. Thus, we reveal previously unappreciated heterogeneity in diverse regulatory programs central to glioblastoma biology, prognosis, and therapy.

Year of Publication
2014
Journal
Science
Volume
344
Issue
6190
Pages
1396-401
Date Published
2014 Jun 20
ISSN
1095-9203
URL
DOI
10.1126/science.1254257
PubMed ID
24925914
PubMed Central ID
PMC4123637
Links
Grant list
R25 NS065743 / NS / NINDS NIH HHS / United States
U54 HG006991 / HG / NHGRI NIH HHS / United States
R01 NS032677 / NS / NINDS NIH HHS / United States
R25NS065743 / NS / NINDS NIH HHS / United States
Howard Hughes Medical Institute / United States
U24 CA180922 / CA / NCI NIH HHS / United States
P50 CA165962 / CA / NCI NIH HHS / United States