MicroRNA-520f regulates EMT, as it activates CDH1 (mRNA) and E-cadherin (protein) expression, and it suppresses tumor cell invasion. We have characterized miR-520f target genes through whole genome transcriptional profiling of miRNA transfected pancreas cancer cells (PANC-1).
miRNA-520f Reverses Epithelial-to-Mesenchymal Transition by Targeting <i>ADAM9</i> and <i>TGFBR2</i>.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma.
Specimen part, Cell line, Time
View SamplesSome commensal bacteria stimulate the immune system but do not present specific antigenicity. Such adjuvant effects have been reported for the bacterial species Lactobacillus plantarum. To study in vivo human responses to L. plantarum, a randomised double-blind placebo-controlled cross-over study was performed. Healthy adults were provided preparations of living and heat-killed L. plantarum bacteria, biopsies were taken from the intestinal mucosa and altered transcriptional profiles were analysed. Transcriptional profiles of human epithelia displayed striking differences upon exposure to living L. plantarum bacteria harvested at different growth phases. Modulation of NF-B-dependent pathways was central among the major altered cellular responses. This unique in vivo study shows which cellular pathways are associated with the induction of immune tolerance in mucosal tissues towards common adjuvanticity possessing lactobacilli.
Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance.
No sample metadata fields
View SamplesProbiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function via largely unknown molecular mechanisms. To explore in vivo mucosal responses of healthy adults to probiotics, we obtained transcriptomes in an intervention study following a double-blind placebo-controlled cross-over design. In the mucosa of the proximal small intestine of healthy volunteers, probiotic strains from the species Lactobacillus acidophilus, L. casei and L. rhamnosus each induced differential gene regulatory networks and pathways in the human mucosa. Comprehensive analyses revealed that these transcriptional networks regulate major basal mucosal processes, and uncovered remarkable similarity to response profiles obtained for specific bioactive molecules and drugs. This study elucidates how intestinal mucosa of healthy humans perceive different probiotics and provides avenues for rationally designed tests of clinical applications.
Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways.
Specimen part
View SamplesThe peroxisome proliferator-activated receptor alpha (PPAR) is a fatty acid-activated transcription factor that governs a variety of biological processes. Little is known about the role of PPAR in the small intestine. Since this organ is frequently exposed to high levels of PPAR ligands via the diet, we set out to characterize the function of PPAR in small intestine using functional genomics experiments and bioinformatics tools. PPAR was expressed at high levels in both human and murine small intestine. Detailed analyses showed that PPAR was expressed highest in villus cells of proximal jejunum. Microarray analyses of total tissue samples revealed, that in addition to genes involved in fatty acid and triacylglycerol metabolism, transcription factors and enzymes connected to sterol and bile acid metabolism, including FXR and SREBP1, were specifically induced. In contrast, genes involved in cell cycle and differentiation, apoptosis, and host defense were repressed by PPAR activation. Additional analyses showed that intestinal PPAR dependent gene regulation occurred in villus cells. Functional implications of array results were corroborated by morphometric data. The repression of genes involved in proliferation and apoptosis was accompanied by a 22% increase in villus height, and a 34% increase in villus area of wild-type animals treated with WY14643. This is the first report providing a comprehensive overview of processes under control of PPAR in the small intestine. We show that PPAR is an important transcriptional regulator in small intestine, which may be of importance for the development of novel foods and therapies for obesity and inflammatory bowel diseases.
Genome-wide analysis of PPARalpha activation in murine small intestine.
Sex, Age, Specimen part
View SamplesGene expression regulation of transporters and phase I/II metabolic enzymes in murine small intestine during fasting
Gene expression of transporters and phase I/II metabolic enzymes in murine small intestine during fasting.
Sex, Age, Specimen part
View SamplesColorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 mol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function.
Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon.
Sex, Age, Specimen part
View SamplesThe skeletal muscle system plays an important role in the independence of older adults. In this study we examine differences in the skeletal muscle transcriptome between healthy young and older subjects and (pre)frail older adults. Additionally, we examine the effect of resistancetype exercise training on the muscle transcriptome in healthy older subjects and (pre)frail older adults. Baseline transcriptome profiles were measured in muscle biopsies collected from 53 young, 73 healthy older subjects, and 61 frail older subjects. Followup samples from these frail older subjects (31 samples) and healthy older subjects (41 samples) were collected after 6 months of progressive resistancetype exercise training. Frail older subjects trained twice per week and the healthy older subjects trained three times per week. At baseline genes related to mitochondrial function and energy metabolism were differentially expressed between older and young subjects, as well as between healthy and frail older subjects. Three hundred seven genes were differentially expressed after training in both groups. Training affected expression levels of genes related to extracellular matrix, glucose metabolism, and vascularization. Expression of genes that were modulated by exercise training was indicative of muscle strength at baseline. Genes that strongly correlated with strength belonged to the protocadherin gamma gene cluster (r=0.73). Our data suggest significant remaining plasticity of ageing skeletal muscle to adapt to resistancetype exercise training. Some agerelated changes in skeletal muscle gene expression appear to be partially reversed by prolonged resistancetype exercise training. The protocadherin gamma gene cluster may be related to muscle denervation and reinnervation in ageing muscle.
Expression of protocadherin gamma in skeletal muscle tissue is associated with age and muscle weakness.
Sex, Specimen part, Subject
View SamplesBackground and Aims: Inflammasome-mediated caspase-1 activity regulates the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1 and IL-18. Recently, we showed that caspase-1 deficiency strongly reduces high fat diet-induced adiposity although the mechanism is still unclear. We now aimed to elucidate the mechanism by which caspase-1 deficiency reduces modulates resistance to high fat diet-feeding fat accumulation in adipose tissue by focusing on the role of caspase-1 in the regulation of triglyceride (TG)-rich lipoprotein metabolism. Methods: Caspase-1 deficient and wild-type mice (both C57Bl/6 background) were used to determine postprandial TG kinetics, intestinal TG absorption, VLDL-TG production as well as TG clearance, all of which strongly contribute to the supply of TG for storage in adipose tissue. Micro-array and qPCR analysis were used to unravel intestinal and hepatic metabolic pathways involved. Results: Caspase-1 deficiency reduced the postprandial response to an oral lipid load, while tissue specific clearance of TG-rich lipoproteins was not changed. Indeed, an oral olive oil gavage containing [3H]TG revealed that caspase-1 deficiency significantly decreased intestinal chylomicron-TG production and reduced the uptake of [3H]TG-derived FA by liver, muscle, and adipose tissue. Similarly, caspase-1 deficiency reduced the hepatic VLDL-TG production without reducing VLDL-apoB production, despite an elevated hepatic TG content. Pathway analysis revealed that caspase-1 deficiency reduces intestinal and hepatic expression of genes involved in lipogenesis. Conclusions: Absence of caspase-1 reduces assembly and secretion of TG-rich lipoproteins, thereby reducing the availability of TG-derived FA for uptake by peripheral organs including adipose tissue. We anticipate that caspase-1 represents a novel link between innate immunity and lipid metabolism.
Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion.
Sex, Specimen part, Disease
View SamplesSuperSeries contain expression data from the nuclei of cell types involved in patterning events, with focus on root apical stem cell formation, at 16-cell stage, early globular stage and late globular stage in the early Arabidopsis embryo (atlas). Expression data comparing nuclear and cellular RNA isolated from whole 16-cell stage Arabidopsis embryos is also included.
Transcriptome dynamics revealed by a gene expression atlas of the early Arabidopsis embryo.
Specimen part
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