|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Patel, 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|
|Journal||Science (New York, N.Y.)|
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.