Iisomer-specific effects of conjugated linoleic (CLA) supplementation on gene expression with particular consideration of the PPAR 2 Pro12Ala SNP in human adipose tissue.
Isomer-specific effects of CLA on gene expression in human adipose tissue depending on PPARgamma2 P12A polymorphism: a double blind, randomized, controlled cross-over study.
Subject
View SamplesExpression of insulin in terminally differentiated non-beta pancreatic cell types could be important for treating type-1 diabetes. We observed that the kinase inhibitor GW8510 up-regulated insulin expression in mouse pancreatic alpha cells.
GW8510 increases insulin expression in pancreatic alpha cells through activation of p53 transcriptional activity.
Cell line, Compound
View SamplesActivity-dependent gene expression is central for sculpting neuronal connectivity in the brain. Despite the importance for synaptic plasticity, a comprehensive analysis of the temporal changes in the transcriptomic response to neuronal activity is lacking. In a genome wide survey we identified genes that were induced at 1, 4, 8, or 24 hours following neuronal activity in the hippocampus.
Genome-wide profiling of the activity-dependent hippocampal transcriptome.
Sex, Age, Specimen part, Time
View SamplesTo identify genes that are regulated from the lncRNA ANRIL (EXON 13), we designed inducible short hairpin RNA constructs and stable integrated them into HEK cells
The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10.
Disease
View SamplesMajor- and minor-group rhinoviruses enter their host by binding to the cell surface molecules ICAM-1 and LDL-R, respectively, which are present on both macrophages and epithelial cells. Although epithelial cells are the primary site of productive HRV infection, previous studies have implicated macrophages in establishing the cytokine dysregulation that occurs during rhinovirus-induced asthma exacerbations. Even though major- and minor-group rhinoviruses are nearly genetically identical, these viruses do not replicate with equal success in monocyte-lineage cell lines. In human primary macrophages, differential mitochondrial activity and signaling pathway activation was observed between major- and minor-group rhinovirus upon initial HRV binding, indicating discordant receptor-dependent response to these rhinovirus types. As well, variances in phosphorylation of kinases (p38, JNK, ERK5) and transcription factors (ATF-2, CREB, CEBP-alpha) were observed between the major- and minor- group HRV treatments. The difference between major- and minor- group HRV activation of signaling pathways was confirmed through RNA-sequencing and observation of differential production of the asthma-relevant cytokines CCL20, CCL2, and IL-10. This is the first report of genetically similar viruses eliciting dissimilar cytokine release, transcription factor phosphorylation, and MAPK activation from macrophages. These results suggest that receptor dependence plays a role in establishing the inflammatory microenvironment initiated in part by monocytic-lineage cells in the human airway upon exposure to rhinovirus. Overall design: RNA sequencing of monocyte-derived macrophages after mock infection or infection by HRV16 or HRV1A
Major and minor group rhinoviruses elicit differential signaling and cytokine responses as a function of receptor-mediated signal transduction.
No sample metadata fields
View SamplesFriedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease usually caused by large homozygous expansions of GAA repeat sequences in intron 1 of the frataxin (FXN) gene. FRDA patients have low FXN mRNA and frataxin protein levels when compared with heterozygous carriers or healthy controls. Presently, there is no effective treatment for FRDA, and biomarkers to measure therapeutic trial outcomes and/or to gauge disease progression are lacking. Peripheral tissues, including blood cells, buccal cells, and skin fibroblasts, can readily be isolated from FRDA patients and used to define molecular hallmarks of disease pathogenesis. However, because these tissues are not directly involved in disease pathogenesis, their relevance as models of the molecular aspects of the disease is yet to be decided. Transcriptome profiling of FRDA skin fibroblasts revealed significantly upregulated expression of genes encoding plasma membrane solute carrier proteins. Conversely, the expression of genes encoding accessory factors and enzymes involved in cytoplasmic and mitochondrial protein synthesis was consistently decreased in the FRDA cells. Finally, comparison of genes differentially expressed in FRDA fibroblasts to 3 previously published gene expression signatures defined for FRDA blood cells showed substantial overlap between the independent datasets, including correspondingly deficient expression of antioxidant defense genes. Together, these results indicate that gene expression profiling of cells derived from peripheral tissues can, in fact, consistently reveal novel molecular pathways of the disease. Overall design: We used RNA sequencing to profile the transcriptomes of primary fibroblast cell lines derived from 18 FRDA patients and 17 unaffected control individuals.
A Comprehensive Transcriptome Analysis Identifies FXN and BDNF as Novel Targets of miRNAs in Friedreich's Ataxia Patients.
Specimen part, Subject
View SamplesThe cytokine IL-10 deactivates macrophages and has been shown to impair resistance to mycobacterial infection. We have infected transgenic mice overexpressing IL-10 under control of the macrophage-specific CD68 promoter (macIL-10tg mice) with Mycobacterium tuberculosis by aerosol and found increased bacterial loads in the lungs of macIL-10tg mice.
Autocrine IL-10 induces hallmarks of alternative activation in macrophages and suppresses antituberculosis effector mechanisms without compromising T cell immunity.
No sample metadata fields
View SamplesThe goal of this experiment was to compare gene expression after t-RA treatment in cells with or without the presence of the PolyADP ribose Glycohydrolase protein (PARG)
Poly (ADP-ribose) glycohydrolase regulates retinoic acid receptor-mediated gene expression.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A tissue-specific landscape of sense/antisense transcription in the mouse intestine.
Specimen part
View SamplesSo far, the annotation of translation initiation sites (TISs) has been based mostly upon bioinformatics rather than experimental evidence. We adapted ribosomal footprinting to puromycin-treated cells to generate a transcriptome-wide map of TISs in a human monocytic cell line. A neural network was trained on the ribosomal footprints at previously annotated AUG translation initiation codons (TICs), and used for the ab initio prediction of TISs in 5062 transcripts with sufficient sequence coverage. Functional interpretation suggested 2994 novel upstream open reading frames (uORFs) in the 5´ UTR (924 AUG, 2070 near-cognate codons), 1406 uORFs overlapping with the coding sequence (116 AUG, 1290 near-cognate) and 546 N-terminal protein extensions (6 AUG, 540 near-cognate). The TIS detection method was validated on the basis of previously published alternative TISs and uORFs. On average, TICs in newly annotated TISs were significantly more conserved among primates than control codons, both for AUGs (p<10-10) and near-cognate codons (p=3.8×10-3). The derived transcriptome-wide map of novel candidate TISs will help to explain how human proteome diversity is influenced by alternative translation initiation and regulation. Overall design: Examination of translational initiation in human cell lines using ribosomal footprinting
Genome-wide search for novel human uORFs and N-terminal protein extensions using ribosomal footprinting.
Cell line, Treatment, Subject
View Samples