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Science DOI:10.1126/science.1254257

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

Publication TypeJournal Article
Year of Publication2014
AuthorsPatel, AP, Tirosh, I, Trombetta, JJ, Shalek, AK, Gillespie, SM, Wakimoto, H, Cahill, DP, Nahed, BV, Curry, WT, Martuza, RL, Louis, DN, Rozenblatt-Rosen, O, Suvà, ML, Regev, A, Bernstein, BE
Date Published2014 Jun 20
KeywordsBrain Neoplasms, Gene Expression Profiling, Genetic Variation, Glioblastoma, Humans, Prognosis, RNA, Messenger, Sequence Analysis, RNA, Single-Cell Analysis

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.


Alternate JournalScience
PubMed ID24925914
PubMed Central IDPMC4123637
Grant ListR25 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