We designed a study to investigate immunoediting of an epithelial cancer genome using wildtype and immunodeficient mice, NGS, and analytical pipelines to process and analyze the data. We carried out experiments with wildtype and immunodeficient RAG1-/- mice with transplanted tumors and analyzed longitudinal samples with respect to the genomic landscape and the immunophenotypes of the tumors. Finally, we performed also experiments with anti-PD-L1 antibodies and show how the activation of the PD1-PD-L1 axis modulates immunoediting. MC38 cells were subcutaneously injected into wild-type C57Bl/6 and immunodeficient Rag1-/- mice. Samples were taken at predefined time points and subjected to detailed analysis, including FACS, exome sequencing, RNA sequencing and SNP arrays. Overall design: Samples were taken at predifined time points, in triplicates and subjected to RNA sequencing using Ion Torrent Proton
Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution.
Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.
Sex, Age, Specimen part, Disease
View SamplesGenome-wide transcriptome analysis of expression changes in Globus Pallidus interna (GPi) from Parkinson's disease brain tissue versus control brain tissue.
PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.
Sex, Specimen part, Disease, Disease stage
View SamplesGenome-wide transcriptome analysis of expression changes in laser-dissected SNpc neurons from Parkinson's disease brain tissue versus control brain tissue.
PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.
Specimen part, Disease, Disease stage
View SamplesSystematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease.
PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.
Age, Specimen part, Disease
View SamplesGenome-wide transcriptome analysis of expression changes in EBV transformed cell lines from the Coriell Cell Repository in Parkinson and Control subjects.
PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.
Sex, Disease, Disease stage
View SamplesSystematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease.
PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.
Sex, Age, Specimen part, Disease
View SamplesAnalysis of substantia nigra from postmortem brains of 4 patients with Parkinsons disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra.
PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.
Sex, Age, Specimen part, Disease
View SamplesExpression data from NIH-3T3 cells left uninfected or infected with MCMV for 2, 4 or 6h on total RNA as well as newly transcribed RNA labeled for 1-2, 3-4, and 5-6hpi. For newly transcribed RNA, the isolated RNA was labeled for 1h and separated from total cellular RNA following Trizol RNA preparation and thiol-specific biotinylation. We used microarrays to analyze the effects of MCMV infection in total and newly transcribed RNA.
Real-time transcriptional profiling of cellular and viral gene expression during lytic cytomegalovirus infection.
Disease, Cell line, Time
View SamplesAlthough the cytokine-inducible transcription factors STAT5a/b promote proliferation of a wide range of cell types, there are cell- and context specific cases in which loss of STAT5a/b results in enhanced cell proliferation. Here we report that loss of STAT5a/b from mouse embryonic fibroblasts (MEFs) leads to enhanced proliferation, which was linked to reduced levels of the cell cycle inhibitor p15INK4B and p21CIP1. We further demonstrate that growth hormone through the transcription factor STAT5a/b enhances expression of the cdkn2B gene and that STAT5a binds to GAS sites within the promoter. We have recently demonstrated that ablation of STAT5a/b from liver results in hepatocellular carcinoma upon a CCl4 insult. We also established that in liver tissue, like in MEFs, STAT5a/b activates expression of the cdkn2B gene. Loss of STAT5a/b led to diminished p15INK4B and increased hepatocyte proliferation. This study for the first time demonstrates that cytokines through STAT5a/b can induce the expression of a key cell cycle inhibitor. These experiments therefore shed a light on the context-specific role of STAT5a/b as tumor suppressors.
The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B negatively regulate cell proliferation through the activation of cyclin-dependent kinase inhibitor 2b (Cdkn2b) and Cdkn1a expression.
Specimen part
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