An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma.

Détails

ID Serval
serval:BIB_B4DE50DE25BB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma.
Périodique
Cell
Auteur⸱e⸱s
Neftel C., Laffy J., Filbin M.G., Hara T., Shore M.E., Rahme G.J., Richman A.R., Silverbush D., Shaw M.L., Hebert C.M., Dewitt J., Gritsch S., Perez E.M., Gonzalez Castro L.N., Lan X., Druck N., Rodman C., Dionne D., Kaplan A., Bertalan M.S., Small J., Pelton K., Becker S., Bonal D., Nguyen Q.D., Servis R.L., Fung J.M., Mylvaganam R., Mayr L., Gojo J., Haberler C., Geyeregger R., Czech T., Slavc I., Nahed B.V., Curry W.T., Carter B.S., Wakimoto H., Brastianos P.K., Batchelor T.T., Stemmer-Rachamimov A., Martinez-Lage M., Frosch M.P., Stamenkovic I., Riggi N., Rheinbay E., Monje M., Rozenblatt-Rosen O., Cahill D.P., Patel A.P., Hunter T., Verma I.M., Ligon K.L., Louis D.N., Regev A., Bernstein B.E., Tirosh I., Suvà M.L.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Statut éditorial
Publié
Date de publication
08/08/2019
Peer-reviewed
Oui
Volume
178
Numéro
4
Pages
835-849.e21
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Diverse genetic, epigenetic, and developmental programs drive glioblastoma, an incurable and poorly understood tumor, but their precise characterization remains challenging. Here, we use an integrative approach spanning single-cell RNA-sequencing of 28 tumors, bulk genetic and expression analysis of 401 specimens from the The Cancer Genome Atlas (TCGA), functional approaches, and single-cell lineage tracing to derive a unified model of cellular states and genetic diversity in glioblastoma. We find that malignant cells in glioblastoma exist in four main cellular states that recapitulate distinct neural cell types, are influenced by the tumor microenvironment, and exhibit plasticity. The relative frequency of cells in each state varies between glioblastoma samples and is influenced by copy number amplifications of the CDK4, EGFR, and PDGFRA loci and by mutations in the NF1 locus, which each favor a defined state. Our work provides a blueprint for glioblastoma, integrating the malignant cell programs, their plasticity, and their modulation by genetic drivers.
Mots-clé
Adolescent, Aged, Animals, Brain Neoplasms/genetics, Brain Neoplasms/pathology, Cell Line, Tumor, Cell Lineage/genetics, Cell Plasticity/genetics, Child, Cohort Studies, Disease Models, Animal, Female, Genetic Heterogeneity, Glioblastoma/genetics, Glioblastoma/pathology, Heterografts, Humans, Infant, Male, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Middle Aged, Mutation, RNA-Seq, Single-Cell Analysis/methods, Tumor Microenvironment/genetics, CDK4, EGFR, NF1, PDGFRA, glioblastoma IDH-wildtype, glioblastoma stem cells, glioblastoma subtypes, lineage tracing, single-cell RNA-sequencing
Pubmed
Web of science
Création de la notice
23/07/2019 11:53
Dernière modification de la notice
19/06/2020 5:21
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