To understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals Overall design: WGBS, RNA-seq, and microarrays were used to study epigenetics and transcriptomics human cancer isolated subcutaneous (abdominal - SA) and vieceral (omental - VA) adipocyte, peripheral blood leukocytes (PBL) and visceral adipose tissue (VAT).
Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes.
Sex, Specimen part, Subject
View SamplesTo understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals Overall design: WGBS, RNA-seq, and microarrays were used to study epigenetics and transcriptomics human cancer isolated subcutaneous (abdominal - SA) and vieceral (omental - VA) adipocyte, peripheral blood leukocytes (PBL) and visceral adipose tissue (VAT).
Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes.
Sex, Specimen part, Subject
View SamplesThe full complement of molecular pathways contributing to Parkinsons disease (PD) pathogenesis remains unknown. Here, to address this issue, we began by using a high-resolution variant of functional magnetic resonance imaging (fMRI) to pinpoint brainstem regions differentially affected by, and resistant to, the disease. Then, relying on the imaging information as a guide, we profiled gene expression levels of postmortem brain samples and used a factorial statistical model to identify a disease related decrease in the expression of the polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1). Next, a series of studies were performed to confirm the pathogenic relevance of this finding. First, to test for a causal link between polyamines and -synuclein toxicity, we investigated a yeast model expressing -synuclein. Polyamines were found to enhance the toxicity of -synuclein, and an unbiased genome-wide screen for modifiers of -synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport. Second, to test for a causal link between SAT1 activity and PD histopathology we investigated a mouse model expressing -synuclein. DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, while Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology. Third, we genotyped PD patients and controls and isolated a rare but novel variant in the SAT1 gene, although the functional significance of this genetic variant was not identified. Taken together, the results suggest that the polyamine pathway contributes to PD pathogenesis.
Polyamine pathway contributes to the pathogenesis of Parkinson disease.
Sex, Age, Subject
View Samplesneuroblastoma cells derived from PDOX models were treated with the kinase inhibitor. Overall design: 5 repetitions of control and IBL-302 treated cells were harvest and submitted for RNAseq analysis
Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma.
Specimen part, Treatment, Subject
View SamplesCD4 T cells can differentiate into a hetergenous population of effector T cells. A population of cytotoxic CD4 T cells can be generated against influenza challenge, however identifying these cells have been challenging. The expression of NKG2A/C/E on CD4 T cells identifies CD4 T cells with cytotoxic potential thus allowing further characterization of this subset of CD4 effector cells.
NKG2C/E Marks the Unique Cytotoxic CD4 T Cell Subset, ThCTL, Generated by Influenza Infection.
Specimen part
View SamplesWe have found the existence of two independent populations contributing to the skin-resident macrophage pool based on their different origin. We have analyzed their gene profile by deep-sequencing (RNA-Seq). Analysis of RNA-Seq data revealed a differential expression signature between both subsets of skin macrophages for 744 of 17741 genes compiled (198 of them showing similar normalized expression levels across replicates). We have further characterized their specialized functions related to their different gene profiles. Overall design: Examination of gene profile of 2 different macrophage subsets coexisting in skin under steady state.
Pivotal role for skin transendothelial radio-resistant anti-inflammatory macrophages in tissue repair.
Specimen part, Cell line, Subject
View SamplesAffymetrix gene expression AID-GFP-positive vs AID-GFP-negative
The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia.
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View SamplesCurrently there is a lack of effective therapies which result in long-term durable response for patients presenting with advanced and metastatic clear cell renal cell carcinoma (ccRCC). This is due in part to a lack of molecular factors which can be targeted pharmacologically. In order to identify novel tumor-specific targets, we performed high throughput gene array analysis screening numerous patient ccRCC tumor tissues across all stages of disease, and compared their gene expression levels to matched normal kidney. Our results identify a number of genes which demonstrate tumor-specific overexpression, and may present as novel targets for therapy.
Neuronal pentraxin 2 supports clear cell renal cell carcinoma by activating the AMPA-selective glutamate receptor-4.
Specimen part
View SamplesCurrently there is a lack of effective therapies which result in long-term durable response for patients presenting with anaplastic thyroid carcinoma (ATC), a very rare and lethal variant of thyroid cancer. ATC is resistant to chemotherapy, radiation, and targeted therapies currently available. In an effort to identify novel tumor-specific therapeutic targets, we performed high throughput gene array analysis screening numerous patient ATC tumor tissues, and compared their gene expression levels to matched and unmatched normal thyroid tissue samples.
Aberrant lipid metabolism in anaplastic thyroid carcinoma reveals stearoyl CoA desaturase 1 as a novel therapeutic target.
Specimen part
View SamplesPresently, there is a deficiency of effective therapies designed to target clear cell renal cell carcinoma (ccRCC), with poor prognosis resulting in patients with advanced disease. Additionally, there is a lack of molecular factors which can be remedially targeted resulting in tumor specific inhibition, and therefore current therapeutic approaches often produce adverse side effects in patients. We identified that Stearoyl-CoA desaturase 1 (SCD1) was consistently overexpressed in patient ccRCC samples, and further investigation of SCD1 as a potential molecular target for ccRCC intervention utilizing a SCD1 inhibitor (A939572) resulted in tumor specific growth inhibition and induction of cell death. In order to understand the mechanism by which the SCD1 inhibitor mediated its anti-tumor effects, we performed gene array analysis and compared expression patterns between treated and untreated samples.
Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma.
Cell line, Treatment
View Samples