Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
Authors: Patel, Anoop P. and Tirosh, Itay and Trombetta, John J. and Shalek, Alex K. and Gillespie, Shawn M. and Wakimoto, Hiroaki and Cahill, Daniel P. and Nahed, Brian V. and Curry, William T. and Martuza, Robert L. and Louis, David N. and Rozenblatt-Rosen, Orit and Suvà, Mario L. and Regev, Aviv and Bernstein, Bradley E. Year: 2014 Journal: Science
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.
Notes
Extracted Concepts
- Established glioblastoma subtype classifiers are variably expressed within tumors
- Glioblastoma cells exhibit continuum of stemness-related expression states
- Hypoxia-related transcriptional programs are variably expressed in glioblastoma cells
- Primary glioblastomas contain inherent variability in oncogenic signaling expression
- Proliferation and immune response programs vary across individual glioblastoma cells