| Literature DB >> 31327527 |
Cyril Neftel1, Julie Laffy2, Mariella G Filbin3, Toshiro Hara4, Marni E Shore5, Gilbert J Rahme5, Alyssa R Richman5, Dana Silverbush5, McKenzie L Shaw3, Christine M Hebert5, John Dewitt5, Simon Gritsch5, Elizabeth M Perez5, L Nicolas Gonzalez Castro6, Xiaoyang Lan5, Nicholas Druck7, Christopher Rodman7, Danielle Dionne8, Alexander Kaplan9, Mia S Bertalan9, Julia Small10, Kristine Pelton11, Sarah Becker11, Dennis Bonal12, Quang-De Nguyen12, Rachel L Servis7, Jeremy M Fung7, Ravindra Mylvaganam7, Lisa Mayr12, Johannes Gojo13, Christine Haberler14, Rene Geyeregger15, Thomas Czech16, Irene Slavc13, Brian V Nahed10, William T Curry10, Bob S Carter10, Hiroaki Wakimoto10, Priscilla K Brastianos9, Tracy T Batchelor9, Anat Stemmer-Rachamimov7, Maria Martinez-Lage7, Matthew P Frosch7, Ivan Stamenkovic17, Nicolo Riggi17, Esther Rheinbay18, Michelle Monje19, Orit Rozenblatt-Rosen8, Daniel P Cahill10, Anoop P Patel20, Tony Hunter21, Inder M Verma21, Keith L Ligon22, David N Louis7, Aviv Regev23, Bradley E Bernstein5, Itay Tirosh24, Mario L Suvà25.
Abstract
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.Entities:
Keywords: CDK4; EGFR; NF1; PDGFRA; glioblastoma IDH-wildtype; glioblastoma stem cells; glioblastoma subtypes; lineage tracing; single-cell RNA-sequencing
Mesh：
Year: 2019 PMID： 31327527 PMCID： PMC6703186 DOI： 10.1016/j.cell.2019.06.024
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582