RNAseq analysis was conducted to complement the targeted and untargeted metabolomics analysis of livers overexpressing the CoA-degrading enzyme Nudt7 or GFP (control). Lipid metabolism requires coenzyme A (CoA), which is found in multiple subcellular compartments including the peroxisomes. In the liver, CoA levels are dynamically adjusted between the fed and fasted states. The elevation in CoA levels that occurs during fasting is driven by increased synthesis but also correlates with decreased expression of Nudt7, the major CoA-degrading enzyme in the liver. Nudt7 resides in the peroxisomes and we overexpressed this enzyme in mouse livers to determine its effect on the size and composition of the hepatic CoA pool in the fed and fasted states. Nudt7 overexpression did not change total CoA levels but decreased the concentration of short-chain acyl-CoAs and choloyl-CoA in fasted livers, when endogenous Nudt7 activity was lowest. The effect on these acyl-CoAs correlated with a significant decrease in the hepatic bile acid content and in the rate of peroxisomal fatty acid oxidation, as estimated by targeted and untargeted metabolomics, combined with the measurement of fatty acid oxidation in intact hepatocytes. Identification of the CoA species and metabolic pathways affected the overexpression on Nudt7 in vivo supports the conclusion that the nutritionally-driven modulation of Nudt7 activity could contribute to the regulation of the peroxisomal CoA pool and peroxisomal lipid metabolism. Overall design: Liver mRNA profiles of 4 mice injected with adeno-associated virus to overexpress Nudt7 and 4 mice injected with adeno-associated virus to overexpress GFP (control) were generated by RNAseq using Illumina HiSeq1500
Overexpression of Nudt7 decreases bile acid levels and peroxisomal fatty acid oxidation in the liver.
Specimen part, Cell line, Subject
View SamplesVaccination induces immunostimulatory signals which are often accompanied by regulatory mechanisms such as IL-10, which control T-cell activation and inhibit vaccine-dependent antitumor therapeutic effect. Thus, here we characterized IL-10-producing cells treated with therapeutic vaccines. Although several cell subsets produced IL-10 irrespective of treatment, an early vaccine-dependent induction of IL-10 was detected in dendritic cells (DC). IL-10 production defined a DC population characterized by a poorly mature phenotype, lower expression of T-cell stimulating molecules and upregulation of PD-L1. These IL-10+ DC showed impaired in vitro T-cell stimulatory capacity, which was rescued by incubation with IL-10R and PD-L1-inhibiting antibodies.
IL-10 expression defines an immunosuppressive dendritic cell population induced by antitumor therapeutic vaccination.
Specimen part, Time
View SamplesCancer-associated skeletal muscle fatigue is a common problem in clinical oncology that is often associated with cancer cachexia, but is not exclusively observed in cachectic patients. The majority of breast cancer (BC) patients report muscle fatigue despite cachexia being relatively rare in this patient population. The clinically relevant phenotype of muscle fatigue in the absence of frank cachexia has no established model system and no approved therapeutic agents. Here, we utilize a breast cancer patient-derived orthotopic xenograft (BC-PDOX) model to recapitulate the human phenotype of tumor-induced muscle fatigue without muscle wasting, and utilized RNA-sequencing to identify pathways contributing to this clinically common phenomenon.
Human Breast Cancer Xenograft Model Implicates Peroxisome Proliferator-activated Receptor Signaling as Driver of Cancer-induced Muscle Fatigue.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature.
Sex
View SamplesGenome-wide analysis of transcriptional profiles in children <17 years of age with inflammatory diseases, bacterial or viral infections or with clinical features suggestive of infection.
Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature.
Sex
View SamplesGenome-wide analysis of transcriptional profiles in children <17 years of age with inflammatory diseases, bacterial or viral infections or with clinical features suggestive of infection.
Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature.
Sex
View SamplesGenome-wide analysis of transcriptional profiles in children <17 years of age with inflammatory diseases, bacterial or viral infections or with clinical features suggestive of infection.
Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature.
Sex
View SamplesThis data was used as an example to illustrate a computational method for assessing statistical significance in microarray experiments
Assessing statistical significance in microarray experiments using the distance between microarrays.
No sample metadata fields
View SamplesWe propose a method to compare the location and variability of gene ex-pression between two groups of microarrays using a permutation test based on the pairwise distance between microarrays. The microarrays could be samples from distinct clinical or biological populations or microarrays prepared at two different levels of an experimental factor. For these tests the entire microarray or some pre-specifed subset of genes, not the individual gene, is the unit of analysis. We apply this method to compare results from two dfferent protocols for preparing labeled targets for microarray hybridization and their subsequent gene expression analysis.
Assessing statistical significance in microarray experiments using the distance between microarrays.
No sample metadata fields
View SamplesWe report here the genes that are sequentially expressed in white blood cells from blood and spleen at 2 hours, 2 day,3 days, and 7 days after burn and sham injury or trauma-hemorrhage (T-H) and sham T-H. Includes WBC treated with LPS for 2 hours and 1 day.
Comparison of longitudinal leukocyte gene expression after burn injury or trauma-hemorrhage in mice.
Specimen part, Treatment, Time
View Samples