Oxidative stress is a hallmark of inflammation in infection or sterile tissue injury. We show that partially oxidized phospholipids of microvesicles (MVs) from plasma of patients with rheumatoid arthritis or cells exposed to oxidative stress induce activation of TLR4. MVs from healthy donors or reconstituted synthetic MVs can be converted to TLR4 agonists by limited oxidation, while prolonged oxidation abrogates the activity. Activation by MVs mimics the mechanism of TLR4 activation by LPS. However, LPS and MVs induce significantly different transcriptional response profile in mouse BMDMs with a strong inflammation-resolving component induced by the endogenous signals. MVs thus represent a ubiquitous endogenous danger signal released under the oxidative stress, which underlies the pervasive role of TLR4 signaling in inflammation.
Toll-like receptor 4 senses oxidative stress mediated by the oxidation of phospholipids in extracellular vesicles.
Sex
View SamplesWe used a high-throughput technology, DNA microarray, to screen the entire genome for the changes in gene expression in diseased tissue to characterize Dupuytren's contracture at a molecular level and find genes that are involved in development of the disease.
Microarray analysis of Dupuytren's disease cells: the profibrogenic role of the TGF-β inducible p38 MAPK pathway.
Sex, Specimen part
View SamplessiSTAT3 knockdown of a tamoxifen initiated, transformation inducible, breast cancer model system (MCF10A-ER-Src), with associated controls of EtOH and siNEG treatments.
STAT3 acts through pre-existing nucleosome-depleted regions bound by FOS during an epigenetic switch linking inflammation to cancer.
Cell line, Treatment
View SamplesHuman ILCs are classically categorized into five subsets; cytotoxic CD127-CD94+ NK cells and non-cytotoxic CD127+CD94-, ILC1s, ILC2s, ILC3s and LTi cells. Here, we identify a novel subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs strongly resemble conventional ILC3s in terms of phenotype, transcriptome and cytokine production, but are highly cytotoxic. IL-15 was unable to induce differentiation of CD94+ ILCs towards mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic CD127+ ILC1s or ILC3s with IL-12 induced upregulation of CD94 and cytotoxic activity, effects that were not observed with IL-15 stimulation. Thus, human helper ILCs can acquire a cytotoxic program without differentiating into NK cells.
Identification of human cytotoxic ILC3s.
Specimen part, Subject
View SamplesOVE26 mouse was chosen to study the progressive changes in renal gene expression because it displays the most advanced albuminuria mouse models that assembles advanced human diabetic nephropathy.
Inflammatory gene expression in OVE26 diabetic kidney during the development of nephropathy.
Age, Specimen part
View SamplesTo identify gene(s) that are modified in their relative expression levels in the Potocki-Lupski Syndrome mouse model and map to the rearranged region, i.e. possible candidate genes at the source of the PTLS-like phenotypes shown by the PTLS mouse, we comp
Abnormal social behaviors and altered gene expression rates in a mouse model for Potocki-Lupski syndrome.
No sample metadata fields
View SamplesBackground: Long non-coding RNAs (lncRNAs) are increasingly implicated as gene regulators and may ultimately be more numerous than protein-coding genes in the human genome. Despite large numbers of reported lncRNAs, reference annotations are likely incomplete due to their lower and tighter tissue-specific expression compared to mRNAs. An unexplored factor potentially confounding lncRNA identification is inter-individual expression variability. Here, we characterize lncRNA natural expression variability in human primary granulocytes. Results: We annotate granulocyte lncRNAs and mRNAs in RNA-seq data from ten healthy individuals, identifying multiple lncRNAs absent from reference annotations, and use this to investigate three known features (higher tissue-specificity, lower expression, and reduced splicing efficiency) of lncRNAs relative to mRNAs. Expression variability was examined in seven individuals sampled three times at one or more than one month intervals. We show that lncRNAs display significantly more inter-individual expression variability compared to mRNAs. We confirm this finding in 2 independent human datasets by analyzing multiple tissues from the GTEx project and lymphoblastoid cell lines from the GEUVADIS project. Using the latter dataset we also show that including more human donors into the transcriptome annotation pipeline allows identification of an increasing number of lncRNAs, but minimally affects mRNA gene number. Conclusions: A comprehensive annotation of lncRNAs is known to require an approach that is sensitive to low and tight tissue-specific expression. Here we show that increased inter-individual expression variability is an additional general lncRNA feature to consider when creating a comprehensive annotation of human lncRNAs or proposing their use as prognostic or disease markers. Overall design: We used PolyA+ RNA-seq data from human primary granulocytes of 10 healthy individuals to de novo annotate lncRNAs and mRNAs in this cell type and ribosomal depleted (total) RNA-seq data from seven of these individuals sampled three times to analyze lncRNA amd mRNA expression variability
Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans.
No sample metadata fields
View SamplesWe find that treating mesenchymal NAMEC8 cells with cholera toxin (CTx) to elevate intracellular cAMP levels and activate PKA induces a mesenchymal-to-epithelial transition whereby the cells assume an epithelial state (N8-CTx). NAMEC8 cells undergo epigenetic reprogramming triggered by active PHF2, a histone demethylase, which demethylates H3K9me2 and H3K9me3 regions of epithelial genes silencing in the mesenchymal state Overall design: Performing RNASeq with HMLE (immortalized human mammary epithelial cells), their mesenchymal CD44hi counterparts, NAMEC8 and the CTx-reverted versions of NAMEC8 a.k.a N8-CTx
Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability.
No sample metadata fields
View SamplesObesity is an epidemic health problem worldwide that impacts the risk and prognosis of many diseases. However, not all obese patients have the same risk of developing these disorders. Individuals with peripheral obesity, i.e., fat distributed subcutaneously, are at little or no risk of the common medical complications of obesity, whereas individuals with central obesity, i.e., fat accumulated in visceral depots, are prone to these complications.
Evidence for a role of developmental genes in the origin of obesity and body fat distribution.
Sex, Age, Specimen part
View SamplesWe sought to determine whether Ldh activity in SCC tumors is a marker of the cell type from which these cells arise, or a key metabolic activity important for tumor initiation or progression. Here we show that genetic abrogation of Ldh enzyme activity in HFSC-mediated tumorigenesis had no effect on tumor number, time to tumor formation, tumor proliferation, epithelial to mesenchymal transition in tumors, gene expression in tumors, tumor pathology, or the immune response to tumors. Overall design: Examination of mRNA profile of five LDHA knockout mice vs five wild type (WT) mice using Illumina HiSeq2500.
Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin.
Specimen part, Subject
View Samples