E-MTAB-7777
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-7777 | ExpressionAtlas | 2019-09-04
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-MTAB-7777-analysis-methods.tsv | Tabular | |||
| E-MTAB-7777-analytics.tsv | Tabular | |||
| E-MTAB-7777-atlasExperimentSummary.Rdata | Rdata | |||
| E-MTAB-7777-configuration.xml | Xml | |||
| E-MTAB-7777-g2_g1-mvaPlot.png | Other |
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Project description:We determined the immune cell composition and their gene expression, by performing single-cell RNA sequencing (scRNA-seq), in anti-PD-L1-treated 2F8cis tumors, a hot and immunoresponsive ovarian murine tumor model, and anti-PD-L1-treated 2F8cis/CA-MSC tumors. We also evaluated the ability of hedgehog inhibitor (HHi) therapy to reverse CA-MSC effects. Adipose-derived mesenchymal stem cells (MSC) were cultured with 2F8cis, an ovarian mouse tumor cell line, to generate cancer-associated MSC (CA-MSC). 2F8cis tumor cell alone or 2F8cis/CA-MSCs co-cultured cells at ratio 1:1 were injected into C57BL/6J mice. Tumor infiltrating CD45+ cells were isolated from anti-PD-L1-treated 2F8cis (Group 1, n=3), anti-PD-L1-treated 2F8cis/CA-MSCs (Group 2, n=3), anti-PD-L1+ IPI-926-treated 2F8cis/CA-MSCs (Group 3, n=3) tumors. Samples were labeled with different TotalSeq oligo-conjugated antibodies and loaded into the Chromium instrument (10x Genomics). The resulting barcoded cDNAs were used to construct libraries. Single-cell cDNA libraries were then processed for RNA sequencing using an Illumina NextSeq-500 platform. Anti-PD-L1-treated 2F8cis/CA-MSC tumors showed a high number of Monocytes and macrophages over-expressing Ccr2 and Tgfbi when compared to anti-PD-L1 responsive 2F8cis tumors. Our results also indicated that IPI-926 restored response to anti-PD-L1 therapy decresing the expression of Ccr2 and Tgfbi both in monocytes and macrophages. Our study represents the first detailed analysis generated by RNA-seq technology of 2F8cis/CA-MSC+ enriched tumor transcriptomes, treated with anti-PDL1 alone or in combination with HHi, and compared with anti-PDL1-treated tumors. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles.
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