Consumption of diets rich in fibers has been associated with several beneficial effects on gastrointestinal health. However, detailed studies on the molecular effects of fibers in colon are limited. In this study we investigated and compared the influence of five different fibers on the mucosal transcriptome, and luminal microbiota and SCFA concentrations in murine colon. Mice were fed diets enriched with fibers that differed in carbohydrate composition, namely inulin (IN), oligofructose (FOS), arabinoxylan (AX), guar gum (GG), resistant starch (RS) or a control diet (corn starch) for 10 days. Gene expression profiling revealed the regulation of specific, but also overlapping sets of epithelial genes by each fiber, which on a functional level were mainly linked to cell cycle and various metabolic pathways including fatty acid oxidation, tricarboxylic acid cycle, and electron transport chain. In addition, the transcription factor PPAR was predicted to be a prominent upstream regulator of these processes. Microbiota profiles were distinct per dietary fiber, but the fibers IN, FOS, AX and GG induced a common change in microbial groups. All dietary fibers, except resistant starch, increased SCFA concentrations but to a different extent. Multivariate data integration revealed strong correlations between the expression of genes involved in energy metabolism and the relative abundance of bacteria belonging to the group of Clostridium cluster XIVa, that are known butyrate producers. These findings illustrate the potential of multivariate data analysis to unravel simple relationships in complex systems.
Comparison of the effects of five dietary fibers on mucosal transcriptional profiles, and luminal microbiota composition and SCFA concentrations in murine colon.
Sex, Age, Specimen part
View SamplesConsumption of resistant starch (RS) has been associated with various intestinal health benefits, but knowledge on its effects on global gene expression in the colon is limited. The main objective of the current study was to identify genes affected by RS in the proximal colon to infer which biologic pathways were modulated. Ten 17-wk-old male pigs, fitted with a cannula in the proximal colon for repeated collection of tissue biopsy samples and luminal content, were fed a digestible starch (DS) diet or a diet high in RS (34%) for 2 consecutive periods of 14 d in a crossover design. Analysis of the colonic transcriptome profiles revealed that, upon RS feeding, oxidative metabolic pathways, such as the tricarboxylic acid cycle and -oxidation, were induced, whereas many immune response pathways, including adaptive and innate immune system, as well as cell division were suppressed. The nuclear receptor peroxisome proliferator-activated receptor (PPARG) was identified as a potential key upstream regulator. RS significantly (P < 0.05) increased the relative abundance of several butyrate-producing microbial groups, including the butyrate producers Faecalibacterium prausnitzii and Megasphaera elsdenii, and reduced the abundance of potentially pathogenic members of the genus Leptospira and the phylum Proteobacteria. Concentrations in carotid plasma of the 3 main short-chain fatty acids acetate, propionate, and butyrate were significantly higher with RS consumption compared with DS consumption. Overall, this study provides novel insights on effects of RS in proximal colon and contributes to our understanding of a healthy diet.
Resistant starch induces catabolic but suppresses immune and cell division pathways and changes the microbiome in the proximal colon of male pigs.
Sex, Age, Specimen part
View SamplesThe meningeal space is occupied by a diverse repertoire of innate and adaptive immune cells. CNS injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation in CNS injury remains poorly understood. Here we describe group 2 innate lymphoid cells (ILC2s) as a novel cell type resident in the healthy meninges that is activated following CNS injury. ILC2s are present throughout the naïve mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile relative to lung ILC2s. After spinal cord injury, meningeal ILC2s are activated in an IL-33 dependent manner, producing type 2 cytokines. Using RNAseq, we characterized the gene programs that underlie the ILC2 activation state. Finally, addition of wild type lung-derived ILC2s into the meningeal space of IL-33R-/- animals improves recovery following spinal cord injury. These data characterize ILC2s as a novel meningeal cell type that responds to and functionally affects outcome after spinal cord injury, and could lead to new therapeutic insights for CNS injury or other neuroinflammatory conditions. Overall design: ILC2s were isolated from 10 week C57/Bl6 mice with and without spinal cord injury (1 day post injury). 5 mice were pooled per group, with meninges dissected, digested, and FACs sorted (CD45+/DAPI-/Lin–/St2+/Thy1+) directly into RNA lysis buffer.
Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury.
Age, Specimen part, Cell line, Subject
View SamplesHuman cytomegalovirus induces a pro-inflammatory monocyte following infection. To begin to address how HCMV induces these rapid changes in infected monocytes, we examined the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of pro-inflammatory genes were upregulated within 4 hours post infection.
Transcriptome analysis reveals human cytomegalovirus reprograms monocyte differentiation toward an M1 macrophage.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer.
No sample metadata fields
View SamplesBreast cancer is a genetically and phenotypically complex disease. To understand the role of microRNAs in this molecular complexity, we performed miRNA expression analysis in a cohort of molecularly well-characterized human breast cancer (BC) cell lines to discover miRNAs associated with the most common molecular subtypes and the most frequent genetic aberrations.Using a microarray carrying LNA modified oligonucleotide capture probes (Exiqon), expression levels of 725 human miRNAs were measured in 51 BC cell lines. MiRNA expression was explored by unsupervised cluster analysis and then associated with the molecular subtypes and genetic aberrations commonly present in breast cancer. Unsupervised cluster analysis using the most variably expressed miRNAs divided the 51 BC cell lines into a major and a minor cluster predominantly mirroring the luminal and basal intrinsic subdivision of BC cell lines. One hundred and thirteen miRNAs were differentially expressed between these two main clusters of which half were related to the ER-status of the cell lines. Forty miRNAs were differentially expressed between basal-like and normal-like/claudin-low cell lines. Within the luminal-group of cell lines, 39 miRNAs were associated with ERBB2 overexpression and 24 miRNAs with E-cadherin gene mutations, which are frequent in this subtype of BC cell lines. In contrast, 31 different miRNAs were associated with E-cadherin promoter hypermethylation, which, contrary to E-cadherin mutation, is exclusively observed in BC cell lines that are not of luminal origin. The differential expression of 30 miRNAs were associated with p16INK4 status while only a few differentially expressed miRNAs were associated with BRCA1, or PIK3CA/PTEN, TP53 mutation status of the cell lines (P-value < 0.05). Twelve miRNAs were associated with DNA copy number variation of the respective locus. Luminal-basal and epithelial-mesenchymal associated miRNAs determine the overall subdivision of miRNA transcriptome of BC cell lines. Specific sets of miRNAs were associated with ERBB2 overexpression, p16INK4aor E-cadherin mutation or E-cadherin methylation status, which implies that these miRNAs may contribute to the driver role of the genetic aberrations. Additionally, miRNAs, which are located in a genomic region showing recurrent genetic aberrations, may themselves play a driver role in breast carcinogenesis or contribute to a driver gene in their vicinity. In short, our study provides detailed molecular miRNA portraits of BC cell lines, which can be exploited for functional studies of clinically important miRNAs.
miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs.
Cell line
View SamplesExpression data were used to predict the activity status of diverse pathways, which were compared to Tamoxifen response
Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer.
No sample metadata fields
View SamplesDiminishment of colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an efficient strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here we report the effects of lifelong CR on markers of colonic health in aging mice. We show that 30% energy reduction, as compared to a control (C) and moderate-fat (MF) diet, is associated with attenuated immune-related gene expression and lower levels of bile acids in the colon. Pronounced shifts in microbiota composition, together with lowered plasma levels of interleukin 6, in mice exposed to CR are in line with these findings. Furthermore, expression of genes involved in lipid metabolism was higher upon CR as compared to C and MF, pointing towards efficient regulation of energy metabolism. Switching from CR to an ad libitum MF diet at old age revealed remarkable phenotypic plasticity, although expression of a small subset of genes remained CR-associated. This research demonstrates that CR beneficially affects markers of colonic health in aging mice and as such may attenuate the progressive age-related decline in health.
Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice.
Sex, Specimen part
View SamplesExpression data were used to predict the activity status of diverse pathways, which were compared to Tamoxifen response
Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer.
No sample metadata fields
View SamplesAdult zebrafish are capable of regenerating cardiac tissue following ventricular resection within 30 days. We profiled both small RNA and mRNA expression in uninjured (0dpa), 1, 3, 7, 14, 21 and 30 days post amputation to study biological processes orchestrate each stage of regeneration. Overall design: Small and mRNA gene expression profiling during 0, 1, 3, 7, 14, 21 and 30 days post ventricular resection.
RegenDbase: a comparative database of noncoding RNA regulation of tissue regeneration circuits across multiple taxa.
Specimen part, Cell line, Subject
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