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Series GSE141532 Query DataSets for GSE141532
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
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.
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.
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
Organization name University Children's Hospital Münster
Department Department of Pediatric Hematology and Oncology
Street address Albert-Schweitzer-Campus 1
City Münster
ZIP/Postal code 48149
Country Germany
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (7)
GSM4205759 RosiniD3_48
GSM4205760 Rosini1132_eye
GSM4205761 Rosini1132_lateral
This SubSeries is part of SuperSeries:
GSE141534 Macrophage-Tumor Cell Interaction Promotes ATRT Progression and Chemoresistance
BioProject PRJNA593826
SRA SRP234887

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE141532_RAW.tar 46.1 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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