We demonstrated that, four weeks after the pulmonary artery banding (PAB) operation, rats could be divided into two groups: an F+ group in which the fibrotic area occupied more than 6.5% of the whole area of the heart tissues, and an F- group in which the fibrotic area occupied less than 6.5% of this area.
Fibrosis growth factor 23 is a promoting factor for cardiac fibrosis in the presence of transforming growth factor-β1.
Sex, Specimen part
View SamplesWe report ileal gene expression at diagnosis in a cohort of 210 treatment-naïve patients of pediatric Crohn''s disease and 35 non-IBD controls from the RISK study. After three years of follow-up after diagnosis, 27 of the CD patients progressed to complicated disease (B2 and/or B3). We aim to test whether Transcriptional Risk Scores helps to distinguish between patient subgroups, improving the predictive power gained from Genetic Risk Scores. Overall design: Ileal biopsies were obtained during diagnostic colonoscopies of children and adolescents (<17 years) who presented with symptoms of IBD. Non-IBD control label corresponds to those with suspected IBD, but without inflammation and normal endoscopic findings. Biopsies were stored at -80 degrees.
Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease.
No sample metadata fields
View SamplesMre11, together with Rad50 and Xrs2/NBS, plays pivotal roles in homologous recombination, repair of DNA double strand breaks (DSBs), activation of damage-induced checkpoint, and telomere maintenance. Using DNA microarray assays to analyze yeast mutants (mre11delta, rad50delta, and spo11Y135F) defective for meiotic DSB formation, we demonstrate that the absence of Mre11 in yeast causes specific effects on regulation of a class of meiotic genes for spore development. The transcriptional deficiency was not observed in other DSB mutants such as rad50delta and spo11Y135F, suggesting the transcriptional defect in mre11delta is due to neither lack of meiotic DSB formation, nor disintegrity of Mre11-Rad50-Xrs2 complex.These defects were confirmed by northern and lacZ reporter gene assays.
Mre11 mediates gene regulation in yeast spore development.
No sample metadata fields
View SamplesColon gene expression in human IBD. The three major clinical subsets of Inflammatory Bowel Disease (IBD) include colon-only Crohn's Disease (CD), ileo-colonic CD, and Ulcerative Colitis (UC). These experiments tested differential colon gene expression in these three types of IBD, relative to healthy control samples, and the local degree of mucosal inflammation as measured by the CD Histological Index of Severity (CDHIS). Colon biopsy samples were obtained from IBD patients at diagnosis and during therapy, and healthy controls. The global pattern of gene expression was determined using GeneSpring software, with a focus upon candidate genes identified in a recent genome wide association study in pediatric onset IBD. Data suggested that two of these candidate genes are up regulated in pediatric IBD, partially influenced by local mucosal inflammation.
Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The histone variant H2A.Z promotes initiation of meiotic recombination in fission yeast.
No sample metadata fields
View SamplesMeiotic homologous recombination is a critical DNA-templated event for sexually-reproducing organisms. It is initiated by a programmed formation of DNA double strand breaks (DSBs), mainly formed at recombination hotspots, and is, like all other DNA-related processes, under great influence of chromatin structure. For example, local chromatin around hotspots directly impacts DSB formation. In addition, DSB is proposed to occur in a higher-order chromatin architecture termed axis-loop, in which many loops protrude from proteinaceous axis. Despite many recent insightful studies, still much remains unknown about how meiotic DSBs are generated in chromatin structure. Here, we show that the highly conserved histone H2A variant H2A.Z promotes meiotic DSB formation in fission yeast. Subsequent investigation revealed that H2A.Z is neither enriched around hotspots nor axis sites, and that transcript levels of DSB-promoting factors were maintained in the absence of H2A.Z. Instead, we found that H2A.Z facilitates chromatin binding of various proteins required for DSB formation. Strikingly, artificial tethering of one of such proteins, Rec10, to chromatin partially restored DSB reduction in H2A.Z-lacking cells. Based on these, we conclude that fission yeast H2A.Z promotes initiation of meiotic recombination partly through delivering DSB-related proteins onto chromatin.
The histone variant H2A.Z promotes initiation of meiotic recombination in fission yeast.
No sample metadata fields
View SamplesThe fields of drug discovery and regenerative medicine require large numbers of adult human primary hepatocytes. For this purpose, it is desirable to use hepatocyte-like cells (HLCs) differentiated from human pluripotent stem cells. To develop an efficient HLCs induction method, we constructed a red fluorescent reporter, CYP3A7R, in which DsRed is placed under the transcriptional regulation of CYP3A7 coding for a human fetus-type P450 enzyme. We created transgenic mice using mouse embryonic stem cells (mESCs) carrying a CYP3A7R transgene.
Real-time fluorometric evaluation of hepatoblast proliferation in vivo and in vitro using the expression of CYP3A7 coding for human fetus-specific P450.
Specimen part
View SamplesBrassinosteroids (BRs) are growth-promoting plant hormones that play a role in abiotic stress responses, but molecular modes that enable this activity remain largely unknown. Here we show that BRs participate in the regulation of freezing tolerance. BR signaling-defective mutants of Arabidopsis thaliana were hypersensitive to freezing before and after cold acclimation. The constitutive activation of BR signaling, in contrast, enhanced freezing resistance. Evidence is provided that the BR-controlled basic helixloophelix transcription factor CESTA (CES) can contribute to the constitutive expression of the C-REPEAT/DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR (CBF) transcriptional regulators that control cold responsive (COR) gene expression. In addition, CBF-independent classes of BR-regulated COR genes are identified that are regulated in a BR- and CES-dependent manner during cold acclimation. A model is presented in which BRs govern different cold-responsive transcriptional cascades through the posttranslational modification of CES and redundantly acting factors. This contributes to the basal resistance against freezing stress, but also to the further improvement of this resistance through cold acclimation.
Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants.
Age, Specimen part, Treatment
View SamplesUsing microcell-mediated chromosome transfer (MMCT) into the mouse melanoma cell line, B16F10, we have previously found that human chromosome 5 carries a gene, or genes, that can negatively regulate TERT expression. To identify the gene responsible for the regulation of TERT transcription, we performed cDNA microarray analysis using parental B16F10 cells, telomerase negative B16F10 microcell hybrids with a human chromosome 5 (B16F10MH5), and its revertant clones (MH5R) with reactivated telomerase. Here we report the identification of PITX1, whose restoration leads to the downregulation of mouse tert (mtert) transcription, as a TERT suppressor gene. Additionally, both human TERT (hTERT) and mouse TERT (mtert) promoter activity can be suppressed by PITX1. We showed that three and one binding sites, respectively, within the hTERT and mtert promoters that express a unique conserved region are responsible for the transcriptional activation of TERT. Furthermore, we showed that PITX1 binds to the TERT promoter both in vitro and in vivo. Thus, PITX1 suppresses TERT transcription through direct binding to the TERT promoter, which ultimately regulates telomerase activity.
Identification of PITX1 as a TERT suppressor gene located on human chromosome 5.
Specimen part, Cell line
View SamplesObjective: Long non-coding RNAs (lncRNA) regulate gene transcription and diverse cellular functions. We previously defined a novel core inflammatory and metabolic ileal gene signature in treatment naïve pediatric Crohn Disease (CD), however, genome-wide characterization of lncRNA expression was lacking. We now extend our analyses to define a more comprehensive view that includes lncRNA. Design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 177 ileal biopsies. Co-expression analysis was used to identify functions and tissue-specific expression. RT-PCR was used to test lncRNAs regulation by IL-1ß in Caco-2 enterocytes model. Results: We characterize a widespread dysregulation of 459 lncRNA in the ileum of treatment naïve pediatric CD patients. Unsupervised and supervised classifications using the 459 lncRNA showed comparable patients' grouping as the 2160 dysregulated protein-coding genes, linking lncRNA to CD pathogenesis. Co-expression and functional annotation enrichment analyses across several tissues and cell types showed that the up-regulated LINC01272 is associated with a myeloid pro-inflammatory signature while the down-regulated HNF4A-AS1 exhibits association with an epithelial metabolic signature. We further validated expression and regulation of prioritized lncRNA upon IL-1ß exposure in differentiated Caco-2 cells. Finally, we identified significant correlations between LINC01272 and HNF4A-AS1 expression and more severe mucosal injury. Conclusion: We define differentially expressed lncRNA in the ileum of treatment naive pediatric CD. We show lncRNA utility to correctly classify disease or healthy states and demonstrate their regulation in response to an inflammatory signal. These lncRNA, after mechanistic exploration, may serve as potential new targets for RNA-based interventions. Overall design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 21 days differentiated caco-2 cells
Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease.
Specimen part, Subject
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