|
| Status |
Public on Apr 18, 2020 |
| Title |
Deconvolution of Cell Type-Specific Drug Responses in Human Tumor Tissue with Single-Cell RNA-seq |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Precision oncology requires the timely selection of effective drugs or drug combinations for individual patients. The ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity. Here we combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses in individual patients. We applied this approach to glioblastoma (GBM) and demonstrated that acute slice cultures recapitulate the cellular and molecular features of the originating tumor tissue. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor Panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients, including unexpected effects on the immune microenvironment. We anticipate that this approach will facilitate rapid, personalized drug screening to identify effective therapies for solid tumors.
|
| |
|
| Overall design |
Performed single-cell RNA-seq on biopsies of human glioma surgical specimens and on acute slice cultures of human glioma surgical specimens treated with various drugs
|
| |
|
| Contributor(s) |
Zhao W, Dovas A, Spinazzi EF, Canoll P, Sims PA |
| Citation(s) |
33975634, 38652658 |
| |
| Submission date |
Apr 17, 2020 |
| Last update date |
Jul 31, 2024 |
| Contact name |
Peter A Sims |
| E-mail(s) |
pas2182@columbia.edu
|
| 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 (43)
|
|
| Relations |
| BioProject |
PRJNA625951 |
| SRA |
SRP256920 |
Less...
More...