| RRC ID |
81920
|
| 著者 |
Dini A, Barker H, Piki E, Sharma S, Raivola J, Murumägi A, Ungureanu D.
|
| タイトル |
A multiplex single-cell RNA-Seq pharmacotranscriptomics pipeline for drug discovery.
|
| ジャーナル |
Nat Chem Biol
|
| Abstract |
The gene-regulatory dynamics governing drug responses in cancer are yet to be fully understood. Here, we report a pipeline capable of producing high-throughput pharmacotranscriptomic profiling through live-cell barcoding using antibody-oligonucleotide conjugates. This pipeline combines drug screening with 96-plex single-cell RNA sequencing. We show the potential of this approach by exploring the heterogeneous transcriptional landscape of primary high-grade serous ovarian cancer (HGSOC) cells after treatment with 45 drugs, with 13 distinct classes of mechanisms of action. A subset of phosphatidylinositol 3-OH kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) inhibitors induced the activation of receptor tyrosine kinases, such as the epithelial growth factor receptor (EGFR), and this was mediated by the upregulation of caveolin 1 (CAV1). This drug resistance feedback loop could be mitigated by the synergistic action of agents targeting PI3K-AKT-mTOR and EGFR for HGSOC with CAV1 and EGFR expression. Using this workflow could enable the personalized testing of patient-derived tumor samples at single-cell resolution.
|
| 巻・号 |
21(3)
|
| ページ |
432-442
|
| 公開日 |
2025-3-1
|
| DOI |
10.1038/s41589-024-01761-8
|
| PII |
10.1038/s41589-024-01761-8
|
| PMID |
39482470
|
| PMC |
PMC11867973
|
| MeSH |
Antineoplastic Agents* / pharmacology
Cell Line, Tumor
Drug Discovery* / methods
ErbB Receptors / metabolism
Female
Humans
Ovarian Neoplasms* / drug therapy
Ovarian Neoplasms* / genetics
Ovarian Neoplasms* / metabolism
Ovarian Neoplasms* / pathology
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / metabolism
RNA-Seq* / methods
Single-Cell Analysis* / methods
Single-Cell Gene Expression Analysis
TOR Serine-Threonine Kinases / antagonists & inhibitors
TOR Serine-Threonine Kinases / metabolism
|
| IF |
12.587
|
| リソース情報 |
| ヒト・動物細胞 |
JHOS-2(RCB1521) |
