This SuperSeries is composed of the SubSeries listed below.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part, Subject
View SamplesEpigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part
View SamplesPreviously, we constructed a coculture model to analyze the effect of macrophages on intestinal epithelial cells, and found that TNF-a secreted from human macrophage-like THP-1 cells induced cell damage to intestinal epithelial Caco-2 cells (Exp.Cell.Res. 2006, 312(19):3909-19). In this study, we present activation of NF-kB in Caco-2 cells within 15 min after coculturing. To reveal how TNF-a secreted from THP-1 cells affects Caco-2 cells in an early stage of coculture, we exhaustively analyzed the changes of gene expression in Caco-2 cells cocultured with THP-1 cells over the time periods of 0, 1, 3, 6, 24, and 48 h by using a DNA microarray. Differentially expressed genes extracted with maSigPro demonstrated that IEX-1 was the lowest p-value gene, that is, the most significantly changed gene among the up-regulated genes. The genes expressed in a similar pattern to IEX-1 involved immunity, apoptosis, and protein kinase cascade. These findings suggest that the stimuli of TNF-a from THP-1 cells activates NF-kB, leading induction of various gene expression. This pattern of gene expression indicates that not only early defense response but also cell death occurs at the same time, causing inflammatory condition.
Transient up-regulation of immunity- and apoptosis-related genes in Caco-2 cells cocultured with THP-1 cells evaluated by DNA microarray analysis.
Cell line, Time
View SamplesWe created a rat renal congestion model and investigated the effect of renal congestion on hemodynamics and molecular mechanisms. The inferior vena cava (IVC) between the renal veins was ligated by suture in male Sprague-Dawley rats to increase upstream IVC pressure and induce congestion in the left kidney only. Left kidney congestion reduced renal blood flow, glomerular filtration rate, and increased renal interstitial hydrostatic pressure. Tubulointerstitial and glomerular injury and medullary thick ascending limb hypoxia were observed only in the congestive kidneys. Molecules related to extracellular matrix expansion, tubular injury, and focal adhesion were upregulated in microarray analysis. Renal decapsulation ameliorated the tubulointerstitial injury. Electron microscopy captured pericyte detachment in the congestive kidneys. Transgelin and platelet-derived growth factor receptors, as indicators of pericyte-myofibroblast transition, were upregulated in the pericytes and the adjacent interstitium. With the compression of the peritubular capillaries and tubules, hypoxia and physical stress induce pericyte detachment, which could result in extracellular matrix expansion and tubular injury in renal congestion.
Pathophysiological and molecular mechanisms involved in renal congestion in a novel rat model.
Sex, Specimen part
View SamplesThe purpose of this experiment was to compare the gene expression pattern between wild-type and Trib1-deficient macrophages in response to LPS.
Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells.
Specimen part
View SamplesIt remains controversial whether human induced pluripotent stem cells (hiPSCs) are distinct from human embryonic stem cells (hESCs) in their molecular signatures and differentiation properties. We examined the gene expression and DNA methylation of 49 hiPSC and 10 hESC lines and identified no molecular signatures that distinguished hiPSCs from hESCs. Comparisons of the in vitro directed neural differentiation of 40 hiPSC and four hESC lines showed that most hiPSC clones were comparable to hESCs. However, in seven hiPSC clones, significant amount of undifferentiated cells persisted even after neural differentiation and resulted in teratoma formation when transplantated into mouse brains. These differentiation-defective hiPSC clones were marked by higher expression of several genes, including those expressed from long terminal repeats of human endogenous retroviruses. These data demonstrated that many hiPSC clones are indistinguishable from hESCs, while some defective hiPSC clones need to be eliminated prior to their application for regenerative medicine.
Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells.
Specimen part
View SamplesBackground: Skeletal muscle constitutes a significant portion of total body mass and is a major regulator of systemic metabolism as it serves as the major site for glucose disposal and the main reservoir for amino acids. With aging, cachexia, starvation, and myositis, there is a preferential loss of fast glycolytic muscle fibers. We previously reported a mouse model in which a constitutively-active Akt transgene is induced to express in a subset of muscle groups leading to the hypertrophy of type IIb myofibers with an accompanying increase in strength. This muscle growth protects mice in various cardio-metabolic disease models, but little is known about the underlying cellular and molecular mechanisms by which fast-twitch muscle impacts disease processes and regulates distant tissues. Purpose: In the present study, poly(A)+ tail mRNA-seq was performed to characterize the transcriptome of the hypertrophic gastrocnemius muscle from Akt1-transgenic mice. Results: Pathway analysis for the 3,481 differentially expressed genes in muscle identified enriched signaling pathways involving growth, cell cycle regulation, and inflammation. Combined metabolomics and transcriptomic analyses revealed that Akt1-induced muscle growth mediated a metabolic shift involving reductions in glycolysis and oxidative phosphorylation, but enhanced pentose phosphate pathway activation and increased branch chain amino acid accumulation. Signal peptide prediction analysis revealed 241 differentially expressed in muscle transcripts that potentially encode secreted proteins. A number of these secreted factors have signaling properties that are consistent with the myogenic, metabolic and cardiovascular-protective properties that have previously been associated with type IIb muscle growth. Conclusions: These data reveal that enhanced Akt signaling promotes the activation of the pentose phosphate and the accumulation of branched amino acids that are important for the production of nucleic acids and proteins. Numerous known and novel transcripts potentially encoding muscle secreted proteins were identified, indicating the importance of fast-twitch muscle in inter-tissue communication. Overall design: mRNA profiles of adult muscle growth from four muscle-specific conditional Akt transgenic (DTG) and four littermate control mice (1256[3Emut]Mck-rtTA) were generated by deep sequencing using Illumina HiSeq.
RNA-seq and metabolomic analyses of Akt1-mediated muscle growth reveals regulation of regenerative pathways and changes in the muscle secretome.
Age, Specimen part, Cell line, Subject
View SamplesIn the present study, we hypothesized that C/EBPa (CCAAT/enhancer-binding protein alpha) plays a role in cell regeneration in response to bronchiolar epithelial cell injury. C/EBPa mediated ciliated cell regeneration after naphthalene bronchiolar epithelial cell injury in vivo. Furthermore, we demonstrated that C/EBPa regulates protease/anti-protease balance after lung injury, and intratracheal treatment with anti-protease (BPTI) restored ciliated cell regeneration after naphthalene injury in CebpaD/D mice.
CCAAT/enhancer binding protein-α regulates the protease/antiprotease balance required for bronchiolar epithelium regeneration.
Specimen part, Treatment
View SamplesSeed development is sensitive to parental dosage, with excess maternal or paternal genomes creating reciprocal phenotypes. Paternal genomic excess results in extensive endosperm proliferation without cellularization and eventual seed abortion. We previously showed that loss of the RNA POL IV gene nrpd1 in tetraploid fathers represses seed abortion in paternal excess crosses. Here we show genetically that RNA-directed DNA methylation (RdDM) pathway activity in the paternal parent is sufficient to determine the viability of paternal excess seeds. The status of the RdDM pathway in paternal excess endosperm does not impact seed viability. Comparison of endosperm transcriptomes, DNA methylation, and small RNAs from balanced and paternal excess endosperm demonstrates that paternal excess seed abortion is unlikely to be dependent on either transposable element or imprinted gene mis-regulation. We suggest instead that loss of paternal RdDM modulates expression at a small subset of genes and desensitizes endosperm to paternal excess. Finally, using allele-specific transcription data, we present evidence of a transcriptional buffering system that up37 regulates maternal alleles and represses paternal alleles in response to excess paternal genomic dosage. These findings prompt reconsideration of models for dosage sensitivity in endosperm. Overall design: Examination of parent-of-origin specific and total gene expression in wild type and nrpd1 endosperm 6 days after pollination - 10 samples. Balanced (Replicate1) GSM2858422 Balanced (Replicate2) GSM2858423 Balanced (Replicate3) GSM2858424 Balanced (Replicate4) GSM2482916 Balanced (Replicate5) GSM2482917
Paternally Acting Canonical RNA-Directed DNA Methylation Pathway Genes Sensitize Arabidopsis Endosperm to Paternal Genome Dosage.
Subject
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