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| Status |
Public on May 14, 2020 |
| Title |
Macrophage-Tumor Cell Interaction Promotes ATRT Progression and Chemoresistance (GEMM) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Atypical teratoid/rhabdoid tumors (ATRT) are known for their heterogeneity concerning pathophysiology and outcome. However, predictive factors within distinct subgroups still need to be uncovered. Using multiplex immunofluorescent staining and singe-cell RNA sequencing we unraveled distinct compositions of the immunological tumor microenvironment (TME) across ATRT subgroups. CD68+ cells predominantly infiltrate ATRT-SHH and ATRT-MYC and are a negative prognostic factor for patients’ survival. Within the murine ATRT-MYC and ATRT-SHH TME, Cd68+ macrophages are core to intercellular communication with tumor cells. In ATRT-MYC distinct tumor cell phenotypes express macrophage marker genes. These cells are involved in the acquisition of chemotherapy resistance in our relapse xenograft mouse model. In conclusion, the tumor cell-macrophage interaction contributes to ATRT-MYC heterogeneity and tumor recurrence.
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| Overall design |
We used a mouse model, Rosa26-creERT2::Smarcb1fl/fl , to profile the transcriptome of SHH and MYC-ATRT by single cell RNA-sequencing (scRNA-seq). We crossed the Smarcb1 fl/fl strain with a mouse line harboring the CreERT2 coding region under the control of ubiquitous (Rosa26) promoter. Pregnant females were induced with a single intraperitoneal dose (50 mg/kg) of Tamoxifen at 6.5 days post-coitum (post-coital plug observation was considered as day 0.5). All mice were intensively monitored until neurological symptoms indicating tumor growth were observed. Tumors were dispersed into single cells and further processed for scRNA-seq. Quality-filtered sequence data were merged and subjected to dimensionality reduction and cell cycle regression to mitigate the effects of cell cycle heterogeneity. This resulted in a total of 24,199 cells, which represent tumor cells as well as tumor-associated non-tumor cells including immune cells.
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| Contributor(s) |
Kerl K, Melcher V, Graf M, Interlandi M |
| Citation(s) |
31848709 |
| |
| Submission date |
Dec 05, 2019 |
| Last update date |
Aug 13, 2020 |
| Contact name |
Kornelius Kerl |
| E-mail(s) |
kornelius.kerl@ukmuenster.de
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| Organization name |
University Children's Hospital Münster
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| Department |
Department of Pediatric Hematology and Oncology
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| Street address |
Albert-Schweitzer-Campus 1
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| City |
Münster |
| ZIP/Postal code |
48149 |
| Country |
Germany |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (7)
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| This SubSeries is part of SuperSeries: |
| GSE141534 |
Macrophage-Tumor Cell Interaction Promotes ATRT Progression and Chemoresistance |
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| Relations |
| BioProject |
PRJNA593826 |
| SRA |
SRP234887 |
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