Peroxisome proliferator-activated receptor alpha (PPAR) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPAR target gene in liver, but its function in hepatic lipid metabolism is unknown. We investigated the regulation of vanin-1, and total vanin activity, by PPAR in mice and humans. Furthermore, the function of vanin-1 in the development of hepatic steatosis in response to starvation was examined in Vnn1 deficient mice, and in rats treated with an inhibitor of vanin activity. Liver microarray analyses reveals that Vnn1 is the most prominently regulated gene after modulation of PPAR activity. In addition, activation of mouse PPAR regulates hepatic- and plasma vanin activity. In humans, consistent with regulation by PPAR, plasma vanin activity increases in all subjects after prolonged fasting, as well as after treatment with the PPAR agonist fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats induces accumulation of hepatic triglycerides upon fasting. Microarray analysis reveal that the absence of vanin-1 associates with gene sets involved in liver steatosis, and reduces pathways involved in oxidative stress and inflammation. We show that hepatic vanin-1 is under extremely sensitive regulation by PPAR and that plasma vanin activity could serve as a readout of changes in PPAR activity in human subjects. In addition, our data propose a role for vanin-1 in regulation of hepatic TG levels during fasting.
PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism.
Sex, Specimen part, Time
View SamplesLipotoxicity is a metabolic disorder that results from accumulation of lipids, particularly fatty acids, in non-adipose tissue leading to cellular dysfunction, lipid droplet formation, activate the ATF3 stress pathway, induce secretion of inflammatory cytokines, and increase APP. Our observations are consistent with neurovascular lipotoxicity that could play a role in cognitive decline with aging.
Triglyceride-rich lipoprotein lipolysis products increase blood-brain barrier transfer coefficient and induce astrocyte lipid droplets and cell stress.
Specimen part, Treatment
View SamplesTo identify the gene expression profile of enteric glia and assess the transcriptional similarity between enteric and extraenteric glia, we performed RNA sequencing analysis on PLP1-expressing cells in the mouse intestine. This analysis shows that enteric glia are transcriptionally unique and distinct from other cell types in the nervous system. Enteric glia express many genes characteristic of the myelinating glia, Schwann cells and oli- godendrocytes, although there is no evidence of myelination in the murine ENS. Overall design: Total RNA expression profiles of PLP1 expressing enteric glial cells (GFP+) and non-glial cells (GFP-negative) were obtained from the ileum and colon of juvenile PLP1-eGFP transgenic mice.
Enteric glia express proteolipid protein 1 and are a transcriptionally unique population of glia in the mammalian nervous system.
Specimen part, Cell line, Subject
View SamplesEffects of SOCS3 on the transcriptional response of bone marrow-derived macrophages to IL-6.
SOCS3 regulates the plasticity of gp130 signaling.
No sample metadata fields
View SamplesElimination of peripheral retinal axons leads to changes in gene expression in both visual and somatosensory thalamic neurons.
Prenatal thalamic waves regulate cortical area size prior to sensory processing.
Specimen part
View SamplesBiochemical fractionation of HEK293 nuclei and RNA-seq of chromatin-associated and soluble-nuclear RNA. Overall design: Nuclei from three biological replicates were isolated by detergent lysis, fractionated, then three chromatin and three soluble RNA samples were converted to cDNA using Illumina TruSeq stranded protocol, and sequenced on Illumina HiSeq2000
Nuclear Fractionation Reveals Thousands of Chromatin-Tethered Noncoding RNAs Adjacent to Active Genes.
No sample metadata fields
View SamplesMorphogenesis of cellecting duct system within developing mouse kidney is driven by growth at the tips of ureteric epithelium. To characterize the transcription program within the tip compartment, here we performed mRNA-Seq of tip cells (Wnt11RFP+;Hoxb7+ cells) and stalk cells (Wnt11RFP-;Hoxb7GFP+ cells) obtained from mouse embryonic kidney through FACS. We identified tip-specific genes from these data, and verified with in situ hybridization and followed up with mechanistic study for some of the intersting targets. Overall design: Examination of two cell types within the ureteric bud of the developing mouse kidney
Cellular heterogeneity in the ureteric progenitor niche and distinct profiles of branching morphogenesis in organ development.
Cell line, Subject
View SamplesTo investigate the role of CYP2B in lipid metabolism, a Cyp2b triple knockout mouse lacking Cyp2b9, Cyp2b10, and Cyp2b13 was developed using CRISPER/Cas9. Wildtype (WT) and Cyp2b-null mice were fed a normal diet (ND) or a 60% high-fat diet (HFD) for 10 weeks. RNA was extracted from the livers of male and female mice from all treatment groups and used for RNA seqencing. RNAseq data demonstrated that hepatic gene expression in ND-fed Cyp2b-null male mice is similar to HFD-fed WT mice, indicating that Cyp2b-null male mice are reacting as if they are receiving a HFD even if they are not. Gene ontology and KEGG pathways show perturbations in lipid metabolism pathways, including PUFA metabolism, fatty acid elongation, and glycerophospholipid metabolism. Overall design: Use RNA-sequencing to investigate the role of Cyp2b in hight-fat diet-induced obesity on a transcriptomic level, by comparing the livers of WT and Cyp2b-null mice fed a HFD for 10 weeks using Illumina technology.
Cyp2b-null male mice are susceptible to diet-induced obesity and perturbations in lipid homeostasis.
Sex, Specimen part, Cell line, Subject
View SamplesIdentification of gene expressed in the enriched inner medullary collecting duct cells in rat.
Transcriptional profiling of native inner medullary collecting duct cells from rat kidney.
Sex, Age, Specimen part
View SamplesThe phenotypically characterized hTERT immortalized porcine olfactory bulb neuroblast cell line (OBGF400) was subjected to an extensive whole genome-scaled expression profile for establishing their use as an in vitro neuronal disease model system.
Transcriptome profile and cytogenetic analysis of immortalized neuronally restricted progenitor cells derived from the porcine olfactory bulb.
Cell line
View Samples