Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma.

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Abstrakt

Tytuł:: Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma.
Autorzy:: Patel AP; 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.
Tirosh I; Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT), Cambridge, MA 02142, USA.
Trombetta JJ; Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT), Cambridge, MA 02142, USA.
Shalek AK; Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT), Cambridge, MA 02142, USA.
Gillespie SM; 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.
Wakimoto H; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Cahill DP; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Nahed BV; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Curry WT; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Martuza RL; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Louis DN; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Rozenblatt-Rosen O; Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT), Cambridge, MA 02142, USA.
Suvà ML; 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. .
Regev A; 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 BE; 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. .
Źródło:: Science (New York, N.Y.) [Science] 2014 Jun 20; Vol. 344 (6190), pp. 1396-401. Date of Electronic Publication: 2014 Jun 12.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-
MeSH Terms:: Genetic Variation*
Brain Neoplasms/*genetics
Glioblastoma/*genetics
RNA, Messenger/*genetics
Brain Neoplasms/classification ; Brain Neoplasms/drug therapy ; Gene Expression Profiling ; Glioblastoma/classification ; Glioblastoma/drug therapy ; Humans ; Prognosis ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods
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Grant Information:: United States HHMI Howard Hughes Medical Institute; R25NS065743 United States NS NINDS NIH HHS; P50 CA165962 United States CA NCI NIH HHS; R25 NS065743 United States NS NINDS NIH HHS; U54 HG006991 United States HG NHGRI NIH HHS; U24 CA180922 United States CA NCI NIH HHS; R01 NS032677 United States NS NINDS NIH HHS
Molecular Sequence:: GEO GSE57872
Substance Nomenclature:: 0 (RNA, Messenger)
Entry Date(s):: Date Created: 20140614 Date Completed: 20140708 Latest Revision: 20230131
Update Code:: 20240104
PubMed Central ID:: PMC4123637
DOI:: 10.1126/science.1254257
PMID:: 24925914
: Czasopismo naukowe

Pełny tekst

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.
(Copyright © 2014, American Association for the Advancement of Science.)

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