Publication Date:
2014-06-14
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123637/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123637/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Patel, Anoop P -- Tirosh, Itay -- Trombetta, John J -- Shalek, Alex K -- Gillespie, Shawn M -- Wakimoto, Hiroaki -- Cahill, Daniel P -- Nahed, Brian V -- Curry, William T -- Martuza, Robert L -- Louis, David N -- Rozenblatt-Rosen, Orit -- Suva, Mario L -- Regev, Aviv -- Bernstein, Bradley E -- P50 CA165962/CA/NCI NIH HHS/ -- R01 NS032677/NS/NINDS NIH HHS/ -- R25NS065743/NS/NINDS NIH HHS/ -- U24 CA180922/CA/NCI NIH HHS/ -- U54 HG006991/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jun 20;344(6190):1396-401. doi: 10.1126/science.1254257. Epub 2014 Jun 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT), Cambridge, MA 02142, USA. Howard Hughes Medical Institute Chevy Chase, MD 20815, USA. ; Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT), Cambridge, MA 02142, USA. ; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT), Cambridge, MA 02142, USA. Howard Hughes Medical Institute Chevy Chase, MD 20815, USA. ; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. ; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. ; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT), Cambridge, MA 02142, USA. bernstein.bradley@mgh.harvard.edu aregev@broadinstitute.org suva.mario@mgh.harvard.edu. ; Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT), Cambridge, MA 02142, USA. Howard Hughes Medical Institute Chevy Chase, MD 20815, USA. Department of Biology, MIT, Cambridge, MA 02139, USA. bernstein.bradley@mgh.harvard.edu aregev@broadinstitute.org suva.mario@mgh.harvard.edu. ; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT), Cambridge, MA 02142, USA. Howard Hughes Medical Institute Chevy Chase, MD 20815, USA. bernstein.bradley@mgh.harvard.edu aregev@broadinstitute.org suva.mario@mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24925914" target="_blank"〉PubMed〈/a〉
Keywords:
Brain Neoplasms/classification/drug therapy/*genetics
;
Gene Expression Profiling
;
*Genetic Variation
;
Glioblastoma/classification/drug therapy/*genetics
;
Humans
;
Prognosis
;
RNA, Messenger/*genetics
;
Sequence Analysis, RNA/methods
;
Single-Cell Analysis/methods
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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