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 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
View SamplesThe establishement of the first plant tissues occurs during embryo development. Indeed, cell types that will form the Arabidopsis root stem cell niche are first specified during 16-cell (16C), early globular (EG) and late globular (LG) stage of embryonic development. While some regulatory factors are known, we do not yet understand the genetic networks underlying the specification of these cell types. One main reason for this is the difficulties in adapting genome-wide approaches to the cellular level. Here, we have adapted such an approach (INTACT) to generate microarray-based cell type-specific transcriptomic profiles at 16C to LG stage for use in determining the role of the transcriptome in cell specification and differentiation during root stem cell niche formation.
Transcriptome dynamics revealed by a gene expression atlas of the early Arabidopsis embryo.
Specimen part
View SamplesMicroarrays were used to analyze the gene expression in endoscopic-derived intestinal mucosal biopsies from patients with inflammatory bowel disease (IBD) and controls
Strong Upregulation of AIM2 and IFI16 Inflammasomes in the Mucosa of Patients with Active Inflammatory Bowel Disease.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative "-Omics" Analysis in Primary Human Hepatocytes Unravels Persistent Mechanisms of Cyclosporine A-Induced Cholestasis.
Specimen part, Treatment, Time
View SamplesCyclosporine A (CsA), is an endecapeptide with strong immunosuppressant activities and has contributed significantly towards clinical progress in organ transplantation. Furthermore, it has various toxic effects in the kidney and especially in the liver where it may induce cholestasis. The CsA drug-induced cholestasis (DIC) pathway includes important genes involved in the uptake, synthesis, conjugation and secretion of bile acids, which can be verified also in hepatic models in vitro. However, whether changes in CsA-induced cholestasis pathway induced in vitro are persistent thus presenting important biomarkers for repeated dose toxicity, has not yet been investigated. We therefore performed multiple -omics analyses, including whole genome analysis of DNA methylation, gene expression and microRNA expression in primary human hepatocytes (PHH) cultured in sandwich configuration, during and after terminating CsA treatment. For this, cells were exposed to a non-cytotoxic dose of 30 M CsA daily for 3 and 5 days. To investigate the persistence of induced changes upon terminating the CsA exposure of 5 days, a subset of PHH was subjected to a washout period (WO-period) of three days. DNA methylation (using NimbleGen 2.1 deluxe promoter arrays), transcriptomic (using Affymetrix Human Genome U133 Plus 2.0 arrays) and microRNA (using Agilent Sureprint G3 Unrestricted Human miRNA V16 8 60 K microarrays) analyses were performed on days 3, 5 and 8. Identification of differentially methylated genes (DMGs), differentially expressed genes (DEGs), and differentially expressed microRNAs (DE-miRs) was performed using several R packages. DMGs, DEGs and DE-miRs were found after CsA treatment of PHH for 3 and 5 days as well after the WO-period. Interestingly, 828 persistent DEGs and 6 persistent DE-miRs, but no persistent DMGs, were found after the WO-period. These persistent DEGs and DE-miRs showed concordance for 22 genes (13 genes upregulated in gene expression and downregulated in microRNA expression; 9 genes downregulated in gene expression and upregulated in microRNA expression). Some of the persistent transcriptomic changes as well as DE-miRs could be successfully mapped onto the DIC pathway, while epigenetic changes not. Furthermore, 29 persistent DEGs in vitro showed changes in the same direction as observed in livers from cholestasis patients. None of those 29 DEGs were present in the DIC pathway or cholestasis adverse outcome pathway. We have for the first time demonstrated a persistent impact of gene expression and microRNA expression related to DIC after repeated dose administration of CsA in vitro.
Integrative "-Omics" Analysis in Primary Human Hepatocytes Unravels Persistent Mechanisms of Cyclosporine A-Induced Cholestasis.
Specimen part, Treatment, Time
View SamplesThe intercalated disc of cardiac myocytes is emerging as a crucial structure in the heart. Loss of intercalated disc proteins like N-cadherin causes lethal cardiac abnormalities, mutations in intercalated disc proteins cause human cardiomyopathy. A comprehensive screen for novel mechanisms in failing hearts demonstrated that expression of the lysosomal integral membrane protein-2 (LIMP-2) is increased in cardiac hypertrophy and heart failure in both rat and human myocardium. Complete loss of LIMP-2 in genetically engineered mice did not affect cardiac development; however these LIMP-2 null mice failed to mount a hypertrophic response to increased blood pressure but developed cardiomyopathy. Disturbed cadherin localization in these hearts suggested that LIMP-2 has important functions outside lysosomes. Indeed, we also find LIMP-2 in the intercalated disc, where it associates with cadherin. RNAi-mediated knockdown of LIMP-2 decreases the binding of phosphorylated b-catenin to cadherin, while overexpression of LIMP-2 has the opposite effect. Taken together, our data show that lysosomal integrated membrane protein-2 is crucial to mount the adaptive hypertrophic response to cardiac loading. We demonstrate a novel role for LIMP-2 as an important mediator of the intercalated disc.
Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy.
No sample metadata fields
View SamplesBackground: The prevalence of type 2 diabetes has increased dramatically in recent decades. Increasing brown adipose tissue (BAT) mass and activity has recently emerged as an interesting approach to not only increase energy expenditure, but also improve glucose homeostasis. BAT can be recruited by prolonged cold exposure in lean, healthy humans. Here, we tested whether cold acclimation could have therapeutic value for patients with type 2 diabetes by improving insulin sensitivity. Methods: Eight type 2 diabetic patients (age 59.35.8 years, BMI 29.83.2 kg/m2) followed a cold acclimation protocol, consisting of intermittent cold exposure (6 hours/day, 14-14.5 C) for 12 consecutive days. Before and after cold acclimation, cold-induced BAT activity was assessed by [18F]FDG-PET/CT scanning, insulin sensitivity at thermoneutrality by a hyperinsulinemic-euglycemic clamp, and muscle and WAT biopsies were taken. Results: Cold-induced BAT activity was low, but increased in all patients upon cold acclimation (SUV from 0.400.29 to 0.630.78, p<0.05). Interestingly, insulin sensitivity showed a very pronounced 40% increase upon cold acclimation (glucose rate of disappearance from 14.94.1 to 20.56.9 mol kg-1 min-1, p<0.05). A 40% increase in insulin sensitivity cannot be explained by BAT glucose uptake, in fact basal skeletal muscle GLUT4 content and translocation was markedly increased after cold acclimation, without effects on insulin signaling or AMPk activation. Conclusions: Regular mild cold exposure has marked effects on insulin sensitivity, which are accompanied by small increases in BAT activity and more pronounced effects on skeletal muscle. These data suggest a novel therapeutic option for the treatment of type 2 diabetes.
Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus.
Subject
View SamplesHematopoietic stem cells (HSCs) are generated via a natural transdifferentiation process known as endothelial-to-hematopoietic cell transition (EHT). Due to small numbers of embryonal arterial cells undergoing EHT and the paucity of markers to enrich for hemogenic endothelial cells, the genetic program driving HSC emergence is largely unknown. Here, we use a highly sensitive RNAseq method to examine the whole transcriptome of small numbers of enriched aortic HSCs (CD31+cKit+Ly6aGFP+), hemogenic endothelial cells (CD31+cKit-Ly6aGFP+) and endothelial cells (CD31+cKit-Ly6aGFP-). Overall design: Comparison of mRNA profiles of endothelial cells, hemogenic endothelial cells, and hematopoietic stem cells generated by deep-sequencing of sorted populations from pool of embryos, in triplicate.
Whole-transcriptome analysis of endothelial to hematopoietic stem cell transition reveals a requirement for Gpr56 in HSC generation.
No sample metadata fields
View SamplesEarly during culture of primary mouse HSCs gene expression changes.
Gene expression profiling of early hepatic stellate cell activation reveals a role for Igfbp3 in cell migration.
Specimen part
View Samples