A phylogenetic analysis of seven different species (human, mouse, rat, worm, fly, yeast, and plant) utilizing all (541) basic helix-loop-helix (bHLH) genes identified, including expressed sequence tags (EST), was performed. A super-tree involving six clades and a structural categorization involving the entire coding sequence was established. A nomenclature was developed based on clade distribution to discuss the functional and ancestral relationships of all the genes. The position/location of specific genes on the phylogenetic tree in relation to known bHLH factors allows for predictions of the potential functions of uncharacterized bHLH factors, including EST's. A genomic analysis using microarrays for four different mouse cell types (i.e. Sertoli, Schwann, thymic, and muscle) was performed and considered all known bHLH family members on the microarray for comparison. Cell-specific groups of bHLH genes helped clarify those bHLH genes potentially involved in cell specific differentiation. This phylogenetic and genomic analysis of the bHLH gene family has revealed unique aspects of the evolution and functional relationships of the different genes in the bHLH gene family. PMID: 18557763
Phylogenetic and expression analysis of the basic helix-loop-helix transcription factor gene family: genomic approach to cellular differentiation.
Sex, Specimen part
View SamplesInflammatory mechanisms have been suggested to play a role in the development of heart failure (HF), but a role for chemokines is largely unknown. The aim of this study was to analyze the role of the chemokine CXCL13 and its receptor CXCR5 in cardiac pathophysiology leading to HF
Lack of chemokine signaling through CXCR5 causes increased mortality, ventricular dilatation and deranged matrix during cardiac pressure overload.
Sex, Specimen part
View SamplesBackground: Cystic fibrosis (CF) is caused by mutations in the CFTR gene that impair function of this cAMP-regulated Cl- channel. In the small intestine, loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have an innate immune response and impaired intestinal transit as well. We investigated whether lubiprostone, which activates the CLC2 Cl- channel, would improve the CF intestinal phenotype.
Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype.
Specimen part, Treatment
View SamplesAffymetrix soybean genome arrays were used to identify genes differentially expressed in the immune resistance response at 6, 12, 24, and 48 hours after inoculation with Phakopsora pachyrhizi isolates TW72-1 or HW94-1
A microarray analysis for differential gene expression in the soybean genome using Bioconductor and R.
No sample metadata fields
View SamplesPurpose: To identify novel genes regulated by the aryl hydrocarbon receptor that influence human Th17 cell function. Methods: Naïve CD4 T cells from peripheral blood of six healthy human volunteers were cultured under four experimental conditions for three days: anti-CD3 and anti-CD28 antibodies (Media control), Media with Th17 conditions (IL-6, TGF-b, IL-1b, IL-23), Th17+FICZ and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. A total of six donors were analyzed. Results: AhR activation with FICZ suppressed IL-17 production from human CD4 T cells and increased IL-22. AhR inhibition with CH223191 potently suppressed IL-22 and modestly increased IL-17 production. On day 3, the number of significantly regulated genes for each treatment were 975 (Th17), 88 (Th17+FICZ) and 142 (Th17+CH223191). 11 common genes were significantly regulated by all three treatments. One of these, GPR68, was investigated further in functional studies since its expression correlated with IL-22 production. Activation of GPR68 with a positive allosteric modulator suppressed IL-22 concentrations in human Th17 cell cultures. Conclusions: Our study demonstrates that GPR68 activation can negatively regulate IL-22 production from human CD4 T cells in the presence of an AhR agonist. RNA-seq is a powerful method to identify novel gene targets that regulate cytokines involved in chronic inflammatory diseases. Overall design: Naïve CD4 T cells were purified from peripheral blood mononuclear cells isolated from six patient samples. Four experimental conditions were created for each sample: media only (control); Th17 differentiated; Th17+FICZ; and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. Differential gene expression analysis identified genes that were expressed at significantly different levels than the control (Media). Ingenuity pathway analysis revealed the most common cellular functions for genes regulated by each treatment.
Cytokine Regulation in Human CD4 T Cells by the Aryl Hydrocarbon Receptor and Gq-Coupled Receptors.
Specimen part, Treatment, Subject
View SamplesAnterior tibialis removed from 3-month old muscle glycogen synthase WT or knockout mouse. RNA was extracted using GibcoBRL TRIzol Reagent and a Quiagen RNeasy kit. Targets were produced using standard Affymetrix procedures from about 5ug of total RNA. GSM40057-GSM40063 AND GSM40956.
Gene expression profiling of mice with genetically modified muscle glycogen content.
No sample metadata fields
View SamplesMale C57Bl/6J mice were fed 45%kcal fat diet (HF) or regular rodent chow (NC) from 4 weeks to 16 weeks of age. Gene expression was compared between RNA obtained from pancreatic islets of HF fed mice and NC mice.
Alterations of pancreatic islet structure, metabolism and gene expression in diet-induced obese C57BL/6J mice.
Specimen part
View SamplesIn this study we present the first genome-wide expression profiling of peripheral B cells by massive parallel RNA sequencing in patients with allergic asthma validating the discovery potential of this approach in allergy. Overall design: RNA-seq was used to asses expression differences in B CD19 Lymphocytes from house dust mite allergic patients and healthy controls.
Genome-wide expression profiling of B lymphocytes reveals IL4R increase in allergic asthma.
No sample metadata fields
View SamplesWe performed RNAseq on subpopulations of mammary epithelial cells. We carried out sorting of a gradient of s-SHIP positive cells in the mammary gland (neg, low, and hi for s-SHIP eGFP). High sSHIP-eGFP populations denote a postulated stem cell population, while low and negative represent more differentiated cell types. s-SHIP eGFP hi to negative potentially represents a gradient from stem to more differentiated progeny, respectively, within the basal epithelial compartment. We FACS sorted 3 replicates for each cell type to represent s-SHIP-neg, s-SHIP-low, and s-SHIP-high. Overall design: We FACS sorted 3 replicates for each cell type to represent s-SHIP-neg, s-SHIP-low, and s-SHIP-high, profiling each of these groups using RNA sequencing.
WNT-Mediated Regulation of FOXO1 Constitutes a Critical Axis Maintaining Pubertal Mammary Stem Cell Homeostasis.
Cell line, Subject
View SamplesPentraxin-2 (PTX-2) is a constitutive, anti-inflammatory, innate immune plasma protein whose circulating level is decreased in chronic human fibrotic diseases. Recent studies indicate that systemic delivery of recombinant PTX-2 inhibits inflammatory diseases associated with fibrosis by blocking pro-fibrotic macrophage activation and promoting anti-inflammatory and regulatory macrophages. Here we show that recombinant human PTX-2 (rhPTX-2) retards the progression of chronic kidney disease in Col4a3 mutant mice that develop Alport syndrome, reducing blood markers of kidney failure, enhancing lifespan by 20%, and improving histological signs of disease. Exogenously-delivered rhPTX-2 is detected in macrophages but is also found in tubular epithelial cells where it counteracts macrophage activation and is cytoprotective for the epithelium. We performed transcriptional profiling of whole kidney homogenates and human proximal tubule epithelial cells (PTECs) to identify pathways differentially activated or suppressed in response to treatment with PTX-2. Computational analysis of genes regulated by rhPTX-2 identified the transcriptional regulator c-Jun and its binding partners, which form AP-1 complexes, as a central target for the function of rhPTX-2. Accordingly, PTX-2 attenuates c-Jun activation and reduces expression of AP-1 dependent inflammatory genes in both monocytes and epithelium. Our studies therefore identify rhPTX-2 as a potential therapy for chronic fibrotic disease of the kidney and an important inhibitor of pathological c-Jun signaling in this setting.
Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease.
Specimen part, Treatment
View Samples