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Series GSE129671 Query DataSets for GSE129671
Status Public on Apr 11, 2022
Title Single-cell based elucidation of molecularly distinct GBM states and drug sensitivity
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Glioblastoma heterogeneity and plasticity remain controversial, with proposed subtypes representing the average of highly heterogeneous admixtures of independent transcriptional states. Single-cell, protein-activity-based analysis identified four novel, molecularly distinct subtypes that successfully harmonize across multiple GBM datasets, including previously published bulk and single-cell profiles and single cell profiles from seven orthotopic PDX models, representative of prior subtype diversity. From these studies, GBM emerges as the plastic equilibrium of single tumor cells coexisting in two mutually-exclusive developmental states, with additional stratification provided by their proliferative potential. Consistent with these findings, all previously proposed subtypes could be recapitulated by mixtures of single cells representing these newly identified states. Most critically, drug sensitivity was predicted and experimentally confirmed as highly state-dependent, both in single-cell assays from patient-derived explants and in PDX models treated with clinically relevant drugs, suggesting that successful therapeutic strategies will likely require combinations of multiple drugs targeting these distinct tumor states.
Overall design Single-cell RNA-sequencing of control and drug-treated slice cultures of human glioma surgical specimens.
Contributor(s) Zhao W, Spinazzi E, Dovas A, Marie T, Upadhyayula P, Bruce J, Canoll P, Sims PA
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Submission date Apr 11, 2019
Last update date Apr 11, 2022
Contact name Peter A Sims
Organization name Columbia University
Street address 3960 Broadway, Lasker 203AC
City New York
State/province NY
ZIP/Postal code 10032
Country USA
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (8)
GSM3719273 PW030-701 (NextSeq)
GSM3719274 PW030-701 (NovaSeq)
GSM3719275 PW030-702 (NextSeq)
BioProject PRJNA532417
SRA SRP192090

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Supplementary file Size Download File type/resource
GSE129671_PW030-701.matrix.txt.gz 38.3 Mb (ftp)(http) TXT
GSE129671_PW030-702.matrix.txt.gz 17.0 Mb (ftp)(http) TXT
GSE129671_PW030-703.matrix.txt.gz 7.4 Mb (ftp)(http) TXT
GSE129671_PW030-705.matrix.txt.gz 8.8 Mb (ftp)(http) TXT
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Raw data are available in SRA
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