HCA Data Explorer

Single cell RNA-seq analysis of adult and paediatric IDH-wildtype Glioblastomas

Updated December 13, 2022

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.

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

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
1Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Institute of Pathology, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, 1011, Switzerland.
2Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel.
3Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA.
4Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
5Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
6Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Departments of Neurology and Radiation Oncology, Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, 02114, USA.
7Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
8Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
9Departments of Neurology and Radiation Oncology, Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, 02114, USA.
10Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA.
11Department of Oncologic Pathology, Brigham and Women's Hospital, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
12Center for Biomedical Imaging in Oncology, Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
13Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, 1090, Austria.
14Institute of Neurology, Medical University of Vienna, Vienna, 1090, Austria.
15Children's Cancer Research Institute (CCRI), St. Anna Kinderspital, Medical University of Vienna, Vienna, 1090, Austria.
16Department of Neurosurgery, Medical University of Vienna, Vienna, 1090, Austria.
17Institute of Pathology, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, 1011, Switzerland.
18Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
19Departments of Neurology, Neurosurgery, Pediatrics and Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
20Department of Neurological Surgery, University of Washington, Seattle, USA.
21Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
22Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Oncologic Pathology, Brigham and Women's Hospital, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
23Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA 02139, USA.
24Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel. Electronic address: Itayt@weizmann.ac.il.
25Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: Suva.Mario@mgh.harvard.edu.
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To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/e4b18cd2-8f15-490d-b9f1-d118aa067dc3
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GEO Series Accessions:

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Analysis Portals

None

Project Label

IdhWildtypeGlioblastomaDiversity

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

brain

Organ Part

9 organ parts

Selected Cell Types

Unspecified

Disease Status (Specimen)

glioblastoma

Disease Status (Donor)

glioblastoma

Development Stage

2 development stages

Library Construction Method

2 library construction methods

Nucleic Acid Source

single cell

Paired End

false, true

Analysis Protocol

analysis_protocol_1, analysis_protocol_2

File Format

2 file formats

Cell Count Estimate

24.1k

Donor Count

29
tsv.gz2 file(s)xlsx2 file(s)