Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma.
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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
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Journal | Science
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Volume | 344
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Issue | 6190
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Pages | 1396-401
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Date Published | 2014 Jun 20
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ISSN | 1095-9203
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URL | |
DOI | 10.1126/science.1254257
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PubMed ID | 24925914
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PubMed Central ID | PMC4123637
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Grant list | R25 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
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