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Series GSE127997 Query DataSets for GSE127997
Status Public on Dec 11, 2020
Title (single-cell RNAseq) An extracellular vesicle-related gene expression signature identifies high-risk patients in medulloblastoma
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Background: Medulloblastoma (MB) is a malignant brain tumor in childhood. It comprises four subgroups with different clinical behaviors. The aim of this study was to characterize the transcriptomic landscape of MB, both at the level of individual tumors as well as in large patient cohorts. Methods: We used a combination of single-cell transcriptomics, cell culture models and biophysical methods such as nanoparticle tracking analysis (NTA) and electron microscopy (EM), to investigate intercellular communication in the MB tumor niche. Results: Tumor cells of the SHH-MB subgroup show a differentiation blockade. These cells undergo extensive metabolic reprogramming. The gene expression profiles of individual tumor cells show a partial convergence with those of tumor-associated glial and immune cells. One possible cause is the transfer of extracellular vesicles (EVs) between cells in the tumor niche. We were able to detect EVs in co-culture models of MB tumor cells and oligodendrocytes. We also identified a gene expression signature, EVS, which shows overlap with the proteome profile of large oncosomes from prostate cancer cells. This signature is also present in MB patient samples. A high EVS expression is one common characteristic of tumors that occur in high-risk patients from otherwise very different MB subgroups or subtypes. Conclusions: With EVS, our study uncovered a novel gene expression signature that has a high prognostic significance across MB subgroups.
Overall design We used a mouse model, Atoh1-cre:SmoM2, to profile the transcriptome of SHH-MB by single cell RNA-sequencing (scRNA-seq). In this system, Atoh1-cre drives expression of a constitutively active Smo allele (SmoM2) in granule neuron precursors (GNPs), resulting in fortuitous activation of downstream target genes and subsequent formation of SHH-MB in the cerebellum. Tumors from four littermates were isolated at postnatal day 20, 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 4,749 cells (mean sequence reads 59,566 ± 7,821 per cell), which represent tumor cells as well as tumor-associated non-tumor cells including immune cells and glia cells.
Contributor(s) Kerl K, Albert T, Interlandi M
Citation(s) 33175161
Submission date Mar 07, 2019
Last update date Mar 12, 2021
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 (4)
GSM3659980 MB 1 (scRNA-seq)
GSM3659981 MB 2 (scRNA-seq)
GSM3659982 MB 3 (scRNA-seq)
This SubSeries is part of SuperSeries:
GSE160003 An extracellular vesicle-related gene expression signature identifies high-risk patients in medulloblastoma
BioProject PRJNA526024
SRA SRP187894

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Supplementary file Size Download File type/resource
GSE127997_RAW.tar 8.6 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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