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.
%0 Journal Article
%1 Patel:2014:Science:24925914
%A Patel, A P
%A Tirosh, I
%A Trombetta, J J
%A Shalek, A K
%A Gillespie, S M
%A Wakimoto, H
%A Cahill, D P
%A Nahed, B V
%A Curry, W T
%A Martuza, R L
%A Louis, D N
%A Rozenblatt-Rosen, O
%A Suvà, M L
%A Regev, A
%A Bernstein, B E
%D 2014
%J Science
%K cancer-research fulltext rna-seq shouldread single-cell-sequencing
%N 6190
%P 1396-1401
%R 10.1126/science.1254257
%T Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
%U https://www.ncbi.nlm.nih.gov/pubmed/24925914
%V 344
%X 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.
@article{Patel:2014:Science:24925914,
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. },
added-at = {2018-12-19T13:59:39.000+0100},
author = {Patel, A P and Tirosh, I and Trombetta, J J and Shalek, A K and Gillespie, S M and Wakimoto, H and Cahill, D P and Nahed, B V and Curry, W T and Martuza, R L and Louis, D N and Rozenblatt-Rosen, O and Suv{\`a}, M L and Regev, A and Bernstein, B E},
biburl = {https://www.bibsonomy.org/bibtex/2e976ea5cfb6dc73e7d461ed9962affeb/marcsaric},
description = {Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. - PubMed - NCBI},
doi = {10.1126/science.1254257},
interhash = {84da9ec67f555ed7148e2155dda78b61},
intrahash = {e976ea5cfb6dc73e7d461ed9962affeb},
journal = {Science},
keywords = {cancer-research fulltext rna-seq shouldread single-cell-sequencing},
month = jun,
number = 6190,
pages = {1396-1401},
pmid = {24925914},
timestamp = {2018-12-19T13:59:39.000+0100},
title = {Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24925914},
volume = 344,
year = 2014
}