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Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma.
|Publication Type||Journal Article|
|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., and Bernstein BE|
|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 (New York, N.Y.)|
|Date Published (YYYY/MM/DD)||2014/06/20|