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| Status |
Public on Jun 24, 2022 |
| Title |
Pro-Inflammatory Cytokines Mediate the Epithelial-to-Mesenchymal-Like Transition of Pediatric Posterior Fossa Ependymoma (single-nucleus RNA-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pediatric ependymoma is a devastating brain cancer marked by its relapsing pattern and lack of effective chemotherapies. This shortage of treatments is due to limited knowledge about ependymoma tumorigenic mechanisms. By means of single-nucleus chromatin accessibility and gene expression profiling of posterior fossa primary tumors and distal metastases, we reveal key transcription factors and enhancers associated with the differentiation of ependymoma tumor cells into tumor-derived cell lineages and their transition into a mesenchymal-like state. We identify NFkB, AP-1, and MYC as mediators of this transition, and show that the gene expression profiles of tumor cells and infiltrating microglia are consistent with abundant pro-inflammatory signaling between these populations. In line with these results, both TGF-b1 and TNF-a induce the expression of mesenchymal genes on a patient-derived cell model, and TGF-b1 leads to an invasive phenotype. Altogether, these data suggest that tumor gliosis induced by inflammatory cytokines and oxidative stress underlies the mesenchymal phenotype of posterior fossa ependymoma.
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| Overall design |
Single-nucleus RNA-seq data was generated from 5 primary, 1 progressive, and 3 metastatic pediatric posterior fossa ependymal tumors using archived flash-frozen tissue.
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| Contributor(s) |
Aubin RG, Troisi EC, Montelongo J, Alghalith AN, Nasrallah MP, Santi M, Camara PG |
| Citation(s) |
35803925 |
| Submission date |
Jun 21, 2022 |
| Last update date |
Jul 20, 2022 |
| Contact name |
Pablo Camara |
| Organization name |
University of Pennsylvania
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| Department |
Genetics
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| Street address |
3700 Hamilton Walk
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE206580 |
Pro-Inflammatory Cytokines Mediate the Epithelial-to-Mesenchymal-Like Transition of Pediatric Posterior Fossa Ependymoma |
|
| Relations |
| BioProject |
PRJNA851411 |
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