Details

Autor(en) / Beteiligte

• Neftel, Cyril
• Laffy, Julie
• Filbin, Mariella G.
• Hara, Toshiro
• Shore, Marni E.
• Rahme, Gilbert J.
• Richman, Alyssa R.
• Silverbush, Dana
• Shaw, McKenzie L.
• Hebert, Christine M.
• Dewitt, John
• Gritsch, Simon
• Perez, Elizabeth M.
• Gonzalez Castro, L. Nicolas
• Lan, Xiaoyang
• Druck, Nicholas
• Rodman, Christopher
• Dionne, Danielle
• Kaplan, Alexander
• Bertalan, Mia S.
• Small, Julia
• Pelton, Kristine
• Becker, Sarah
• Bonal, Dennis
• Nguyen, Quang-De
• Servis, Rachel L.
• Fung, Jeremy M.
• Mylvaganam, Ravindra
• Mayr, Lisa
• Gojo, Johannes
• Haberler, Christine
• Geyeregger, Rene
• Czech, Thomas
• Slavc, Irene
• Nahed, Brian V.
• Curry, William T.
• Carter, Bob S.
• Wakimoto, Hiroaki
• Brastianos, Priscilla K.
• Batchelor, Tracy T.
• Stemmer-Rachamimov, Anat
• Martinez-Lage, Maria
• Frosch, Matthew P.
• Stamenkovic, Ivan
• Riggi, Nicolo
• Rheinbay, Esther
• Monje, Michelle
• Rozenblatt-Rosen, Orit
• Cahill, Daniel P.
• Patel, Anoop P.
• Hunter, Tony
• Verma, Inder M.
• Ligon, Keith L.
• Louis, David N.
• Regev, Aviv
• Bernstein, Bradley E.
• Tirosh, Itay
• Suvà, Mario L.

Titel

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

Ist Teil von

• Cell, 2019-08, Vol.178 (4), p.835-849.e21

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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. [Display omitted] •Four cellular states drive glioblastoma malignant cells heterogeneity•In vivo single-cell lineage tracing supports plasticity between these four states•Genetics and the microenvironment influence the frequency of cells in each state•TCGA subtypes reflect the highest-frequency malignant states and the microenvironment Single-cell analyses of glioblastoma samples reveal multiple cellular states, their plasticity and the genetic underpinnings of state proportions in a given tumor.