Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
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Regev_Single cell rna.pdf
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Author(s)
Patel, A. P.
Tirosh, I.
Trombetta, J. J.
Gillespie, S. M.
Wakimoto, H.
Cahill, D. P.
Nahed, B. V.
Curry, W. T.
Martuza, R. L.
Louis, D. N.
Date Issued
June 2014
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Patel, A. P., I. Tirosh, J. J. Trombetta, A. K. Shalek, S. M. Gillespie, H. Wakimoto, D. P. Cahill, et al. “Single-Cell RNA-Seq Highlights Intratumoral Heterogeneity in Primary Glioblastoma.” Science 344, no. 6190 (June 12, 2014): 1396–1401.
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Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1126/science.1254257
