Polyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double-stranded (ds)RNA, a molecular pattern associated with viral infections, that is used to exacerbate inflammation in lung injury models. Despite its frequent use, there are no detailed studies of the responses elicited by a single topical administration of poly I:C to the lungs of mice. Our data provides the first demonstration that the molecular responses in the airways induced by poly I:C correlate to those observed in the lungs of COPD patients. These expression data also revealed three distinct phases of response to poly I:C, consistent with the changing inflammatory cell infiltrate in the airways. Poly I:C induced increased numbers of neutrophils and NK cells in the airways, which were blocked by CXCR2 and CCR5 antagonists, respectively. Using gene set variation analysis on representative data sets, gene sets defined by poly I:C-induced DEGs were enriched in the molecular profiles of chronic obstructive pulmonary disease (COPD), but not idiopathic pulmonary fibrosis patients. Collectively, these data represent a new approach for validating the clinical relevance of preclinical animal models and demonstrate that a dual CXCR2/CCR5 antagonist may be an effective treatment for COPD patients.
Double-stranded RNA induces molecular and inflammatory signatures that are directly relevant to COPD.
Sex, Specimen part, Time
View SamplesWe compare the transcriptome of two different clones of multipotent adult progenitor cells (MAPCs) using Affymetrix arrays.
Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells.
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View SamplesGenomic profiling of bleomycin- and saline-treated mice across 7 timepoints (1, 2, 7, 14, 21, 28, 35 days post treatment) was carried out in C57BL6/J mice to determine the phases of response to bleomycin treatment which correspond to onset of active pulmonary fibrosis.
Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for "active" disease.
Sex, Specimen part, Treatment, Time
View SamplesMore than 2,000 genes appear to be upregulated or downregulated in skeletal muscle of mice with constitutive knockout of myostatin (Steelman et al., FASEB J 20:580-2, 2006). This study was done to determine whether inhibition of myostatin activity in mature mice has similar effects on the pattern of gene expression.
Stimulation of skeletal muscle myofibrillar protein synthesis, p70 S6 kinase phosphorylation, and ribosomal protein S6 phosphorylation by inhibition of myostatin in mature mice.
No sample metadata fields
View SamplesAnalysis of integrin alpha7 transgenic mice skeletal muscle transcription profiles comparing to wild type controls. Integrin alpha7 is the major laminin binding integrin in muscle cells. Enhancing its expression has been demonstrated to alleviate pathology in a murine model of Duchenne muscular dystrophy. Results of this study provide insights into the effects of increasing integrin alpha7 expression on skeletal muscle transcription and physiology in vivo. This analysis also evaluates any potential possible side effects associate with enhancing integrin alpha7 in skeletal muscle.
Increasing alpha 7 beta 1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression.
Sex, Age, Specimen part
View SamplesHigh-fat diets are associated with increased obesity and metabolic disease in mice and humans. Here we used analysis of variance (ANOVA) to scrutinize a microarray data set consisting of 10 inbred strains of mice from both sexes fed atherogenic high-fat and control chow diets. An overall F-test was applied to the 40 unique groups of strain-diet-sex to identify 15,288 genes with altered transcription. Bootstrapping k-means clustering separated these changes into four strain-dependent expression patterns, including two sex-related profiles and two diet-related profiles. Sex-induced effects correspond to secretion (males) or fat and energy metabolism (females), whereas diet-induced changes relate to neurological processes (chow) or immune response (high-fat). The full set of pairwise contrasts for differences between strains within sex (90 different statistical tests) uncovered 32,379 total changes. These differences were unevenly distributed across strains and between sexes, indicating that strain-specific responses to high-fat diet differ between sexes. Correlations between expression levels and 8 obesity-related traits identified 5,274 associations between transcript abundance and measured phenotypic endpoints. From this number, 2,678 genes are positively correlated with total cholesterol levels and associate with immune-related categories while 2,596 genes are negatively correlated with cholesterol and connect to cholesterol synthesis.
Practical applications of the bioinformatics toolbox for narrowing quantitative trait loci.
Sex
View SamplesTo investigate the early host response triggered by three different strains of Trypanosoma cruzi at a local infection site, changes in host gene expression were monitored in a murine intradermal infection model using Affymetrix oligonucleotide arrays. Robust induction of IFN-stimulated genes (ISGs) was observed in excised skin 24 hours post-infection where the level of ISG induction was parasite strain-dependent with the least virulent strain triggering a muted IFN response. Infection of mice immunodepleted of IFN-producing cells or infection of IFN-deficient mice had minimal impact on the IFN response generated in T. cruzi infected mice. In contrast, infection of mice lacking the type I IFN receptor demonstrated that type I IFNs are largely responsible for the IFN response generated at the site of infection. These data highlight type I IFNs as important components of the innate immune response to T. cruzi the site of inoculation and their role in shaping the early transcriptional response to this pathogen.
Trypanosoma cruzi triggers an early type I IFN response in vivo at the site of intradermal infection.
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View SamplesKey regulators of septum formation between the left and right ventricle in mammals, including the transcription factors TXB5 and PITX2, feature loss-of-function phenotypes that affect development of the two-chambered zebrafish heart, suggesting
Generating and evaluating a ranked candidate gene list for potential vertebrate heart field regulators.
Specimen part
View SamplesThese experiments are designed to discover genes that are expressed selectively by synaptic nuclei in skeletal muscle with the particular goal of identifying genes that regulate motor axon growth and differentiation.
CD24 is expressed by myofiber synaptic nuclei and regulates synaptic transmission.
No sample metadata fields
View SamplesThe p53 family is known as a family of transcription factors with functions in tumor suppression and development. Whereas the central DNA binding domain is highly conserved among the three family members p53, p63 and p73, the C-terminal domains (CTDs) are diverse and subject to alternative splicing and post-translational modification. Here we demonstrate that the CTDs strongly influence DNA binding and transcriptional activity. While p53 and the p73 isoform p73gamma have basic CTDs and form weak sequence-specific protein-DNA complexes, the major p73 isoforms alpha, beta and delta have neutral CTDs and bind DNA strongly. A basic CTD has been previously shown to enable sliding along the DNA backbone and to facilitate the search for binding sites in the complex genome. Our experiments, however, reveal that a basic CTD also reduces protein-DNA complex stability, intranuclear mobility, promoter occupancy in vivo, transgene activation and induction of cell cycle arrest or apoptosis. A basic CTD in p53 and p73gamma therefore provides both positive and negative regulatory functions presumably to enable rapid switching of protein activity in response to stress. In contrast, most p73 isoforms exhibit constitutive DNA binding activity consistent with a predominant role in developmental control.
C-terminal diversity within the p53 family accounts for differences in DNA binding and transcriptional activity.
No sample metadata fields
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