Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neuromuscular disorder characterized by the selective degeneration of upper and lower motor neurons, progressive muscle wasting and paralysis. To define the full set of alterations in gene expression in skeletal muscle during the course of the disease, we performed high-density oligonucleotide microarray analysis of gene expression in hind limb skeletal muscles of sod1(G86R) mice, one of the existing transgenic models of ALS. To monitor denervation-dependent gene expression, we determined the effects of short-term acute denervation on the muscle transcriptome after sciatic nerve axotomy.
Gene profiling of skeletal muscle in an amyotrophic lateral sclerosis mouse model.
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesHere, we examined the role of intestinal epithelial specific tumor suppressive function of 53. We provide evidence that p53 plays a dual role during carcinogen-induced tumorigenesis. At the initiation stage, p53 controls DNA damage and survival of initiated epithelia. In contrast, at later stages, loss of p53 is associated with the formation of an inflammatory microenvironment that is linked to epithelial mesenchymal transition, invasion and metastasis and the activation of NF-kappaB and Stat3. Thus, we propose a novel p53 controlled tumor suppressive function during the progression stage of colorectal cancer that is independent of its well-established role in cell cycle regulation, apoptosis and senescence.
Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and lymph node metastasis of carcinogen-induced colorectal tumors.
Specimen part
View SamplesThe invasion of activated fibroblasts represents a key pathomechanism in fibrotic diseases, carcinogenesis and metastasis. Here, invading fibroblasts contribute to fibrotic extracellular matrix (ECM) formation and the initiation, progression, or resistance of cancer, respectively. To construct a transcriptome-wide signature of fibroblast invasion, we used a multiplex phenotypic 3D invasion assay using murine lung fibroblasts. Microarray-based gene expression profiles of invading and non-invading fibroblasts were highly distinct: 1049 genes were differentially regulated (>1.5-fold). An unbiased pathway analysis (Ingenuity) identified a significant enrichment for the functional clusters invasion of cells, idiopathic pulmonary fibrosis (IPF) and metastasis. Particularly, matrix metalloprotease13 (MMP13), transforming growth factor (TGF)1, Caveolin1 (Cav1), Phosphatase and Tensin Homolog (Pten), and secreted frizzled-related protein1 (Sfrp1) were among the highest regulated genes. In silico analysis by Ingenuity predicted TGF1, epidermal growth factor (EGF), fibroblast growth factor2 (FGF2), and platelet-derived growth factor (PDGF)-BB to induce invasion. As such, these growth factors were tested in the 3D invasion assay and displayed a significant induction of invasion, thus validating the transcriptome profile. Accordingly, our transcriptomic invasion signature describes the invading fibroblast phenotype in unprecedented detail and provides a tool for future functional studies of cell invasion and therapeutic modulation thereof.
Validated prediction of pro-invasive growth factors using a transcriptome-wide invasion signature derived from a complex 3D invasion assay.
Sex
View SamplesRats overexpressing the human renin and angiotensinogen genes die after seven weeks of end organ damage. They develop hypertension, heart hypertrophy and proteinuria.We compared terminal heart failure, these are indeed terminally ill to double transgenic animals suffering on hypertension, proteinuria and heart hypertrophy. In addition, Losartan-treated animals (10 mg/kg/d)showed similar physiological parameters (normotension, no proteinuria and no heart hypertrophy compared to control sprague dawley rats.
Cardiac gene expression profile in rats with terminal heart failure and cachexia.
No sample metadata fields
View SamplesGene expression of P. aerruginosa changes after short-term exposure to ciprofloxacin at sub-inhibitory concentrations but the effect of long-term exposure which select for the most fitted subpopulations is not known.
The phenotypic evolution of Pseudomonas aeruginosa populations changes in the presence of subinhibitory concentrations of ciprofloxacin.
No sample metadata fields
View SamplesWe provide here the alterations in gene expression profiles of HepaRG cells, a validated model for cellular steatosis, exposed to three concentration of the polychlorinated biphenyl (PCB) 126, one of the most potent chemical inducing NAFLD. Additionnally, three concentration of the pesticide active ingredient glyphosate were tested. This ultimately suggested sensitive biomarkers of exposure. A gene ontology analysis showed hallmarks of an activation of the AhR receptor by dioxin-like compounds. Our study provides grounds for the development of molecular signatures of fatty liver diseases to rapidly assess toxic effects of chemicals in the HepaRG cell line. Overall design: Differentiated HepaRGTM cells (HPR 116) were purchased from Biopredic International. The cells were kept in the general purpose medium until day 8, when the culture becomes well organized and includes well-delineated trabeculae and many canaliculi-like structures. Three concentrations of the PCB were then tested from day 8 to day 14, in order to cover a wide range of biological effects, starting from low environmental exposures (100 pM) to high concentrations of (1 uM), with an intermediate concentration (10 nM). Three concentrations of glyphosate, or one concentration of the Roundup herbicide (Grand Travaux +) were also tested in the same system.
Comparison of transcriptome responses to glyphosate, isoxaflutole, quizalofop-p-ethyl and mesotrione in the HepaRG cell line.
Specimen part, Cell line, Treatment, Subject
View SamplesWe provide here the alterations in gene expression profiles of HepaRG cells, a validated model for cellular steatosis, exposed to three concentration of quizalofop-p-ethyl, isoxaflutole and mesotrione Overall design: Differentiated HepaRGTM cells (HPR 116) were purchased from Biopredic International. The cells were kept in the general purpose medium until day 8, when the culture becomes well organized and includes well-delineated trabeculae and many canaliculi-like structures. Three concentrations of the different pesticide active ingredients (quizalofop-p-ethyl, isoxaflutole and mesotrione ) were then tested from day 8 to day 14. In order to ensure coverage of a wide range of potential biological effects, three concentrations of each active principle were tested; a concentration representative of low environmental exposure (0.1 uM), an intermediate concentration (10 uM) and a high concentration (1000 uM).
Comparison of transcriptome responses to glyphosate, isoxaflutole, quizalofop-p-ethyl and mesotrione in the HepaRG cell line.
Specimen part, Cell line, Subject
View SamplesWe provide here the alterations in gene expression profiles of 3T3-L1 cells, a validated model for adipogenesis, exposed to quizalofop-p-ethyl for 6h, 24h and 12 days. Overall design: Exposure to endocrine disrupting chemicals is a risk factor for obesity. The most commonly used pesticide active ingredients have never been tested in an adipogenesis assay. We tested for the first time the lipid accumulation induced by glyphosate, 2,4-dichlorophenoxyacetic acid, dicamba, mesotrione, isoxaflutole and quizalofop-p-ethyl (QpE) in 3T3-L1 adipocytes. Only QpE caused triglyceride accumulation from a concentration of 1 µM. We thus conducted an in-depth investigation of molecular mechanisms responsible for the adipogenic effects of quizalopfop-p-ethyl by an RNA-seq analysis.
Quizalofop-p-Ethyl Induces Adipogenesis in 3T3-L1 Adipocytes.
Specimen part, Cell line, Treatment, Subject
View SamplesUsing measles virus induced T cell suppression as a model, we established that T cell inhibitory protein isoforms can be produced from alternatively spliced pre-mRNAs as a result of virus-mediated ablation of T cell receptor dependent activation of the phosphatidylinositol-3-kinase (PI3K). To asses production of alternative splice variants in response to PI3K abrogation in T cells at a whole cell level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) on T cell suppression. Applying our algorithm on this model 9% of the genes were assigned as AS, while only 3% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulated at the level of AS or RG were found enriched in different functional groups with AS targeting e. g. extra cellular matrix (ECM)-receptor interaction and focal adhesion, while cytokine-receptor interaction, Jak-STAT and p53 pathways were mainly RG. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry strongly supporting the notion that PI3K abrogations interferes with key T cell activation processes at both levels, and that candidates represented within both categories bear the potential to actively contribute to T cell suppression
Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells.
Specimen part, Treatment, Subject
View SamplesMiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are so far hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We identified miRNA-1 as top candidate differentially expressed in tumor and metastasis. Furthermore, miRNA-1 was de-regulated in 16 additional tumor entities underscoring its central role in tumor pathogenesis. Functional analyses showed an additive effect of miRNA-1 with camptothecin treatment. We used a systems-biology simulation of cellular cancer models implemented in PyBios to investigate miRNA-1 function and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options. Overall design: Examination of miRNA expression values by Illumina sequencing of matched benign, tumor and metastasis tissues of 8 colorectal cancer patients. For 4 of these patients all tissues have been resequenced to obtain mRNA expression values.
High-throughput miRNA and mRNA sequencing of paired colorectal normal, tumor and metastasis tissues and bioinformatic modeling of miRNA-1 therapeutic applications.
Sex, Age, Specimen part, Disease, Disease stage, Subject
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