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| 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
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| 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.
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| Overall design |
Single-cell RNA-sequencing of control and drug-treated slice cultures of human glioma surgical specimens.
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| Contributor(s) |
Zhao W, Spinazzi E, Dovas A, Marie T, Upadhyayula P, Bruce J, Canoll P, Sims PA |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Apr 11, 2019 |
| Last update date |
Apr 11, 2022 |
| Contact name |
Peter A Sims |
| E-mail(s) |
pas2182@columbia.edu
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| Organization name |
Columbia University
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| Street address |
3960 Broadway, Lasker 203AC
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA532417 |
| SRA |
SRP192090 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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