Here we harnessed the potential of RNA sequencing in 89 human pancreatic islet donors to identify genes and exons regulated in this relevant tissue for T2D. Overall design: mRNA profiles of 89 human pancreatic islet donors having different levels of blood glucose (HbA1c) with and without T2D. The data was generated by deep sequencing using Illumina HiSeq 2000.
Orphan G-protein coupled receptor 183 (GPR183) potentiates insulin secretion and prevents glucotoxicity-induced β-cell dysfunction.
Sex, Age, Specimen part, Subject
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Reconstructed cell fate-regulatory programs in stem cells reveal hierarchies and key factors of neurogenesis.
Specimen part, Time
View SamplesWe have integrated dynamic RXRa binding, chromatin accessibility and promoter epigenetic status with the transcriptional activity inferred from RNA polymerase II mapping and transcription profiling. This demonstrated a temporal organization structure, in which early events are preferentially enriched for common GRNs, while cell fate specification is reflected by the activation of late programs in a cell-type specific manner. Furthermore, significant differences in cell lines' promoter status of genes associated with cell-line specific programs were inferred. Finally, a variety of transcription factors (TFs) playing a direct role in the signal transduction cascade downstream of the RXR/RAR initiated wiring were identified, several of them commonly regulated in both model systems, but in addition cell-type specific TF drivers were also identified.
Reconstructed cell fate-regulatory programs in stem cells reveal hierarchies and key factors of neurogenesis.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tribbles 3: a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide.
Specimen part, Cell line
View SamplesThis study set out to identify global changes in gene expression in human embryonic kidney (HEK) cells stably transfected with Toll-like receptor 2 (TLR2) over a 48 hour time-course, following stimulation with 10 g/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori.
Tribbles 3: a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide.
Specimen part
View SamplesThis study set out to identify global changes in gene expression in AGS gastric epithelial cells following 8 hours stimulation with 10 g/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori.
Tribbles 3: a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide.
Specimen part, Cell line
View SamplesThis study set out to identify global changes in gene expression in MKN45 gastric epithelial cells following 8 hours stimulation with 10 g/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori.
Tribbles 3: a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide.
Specimen part, Cell line
View SamplesFailure of molecular chaperones to direct the correct folding of newly synthesized proteins leads to the accumulation of misfolded proteins in cells. HSPA4 is a member of the heat shock protein 110 family (HSP110) that acts as a nucleotide exchange factor of HSP70 chaperones. We found that the expression of HSPA4 is upregulated in murine hearts subjected to pressure overload and in failing human hearts. To investigate the cardiac function of HSPA4, Hspa4 knockout (KO) mice were generated and exhibited cardiac hypertrophy and fibrosis. Hspa4 KO hearts were characterized by a significant increase in heart weight/body weight ratio, elevated expression of hypertrophic and fibrotic gene markers, and concentric hypertrophy with preserved contractile functions. Cardiac hypertrophy in Hspa4 KO hearts was associated with enhanced activation of gp130-STAT3, CaMKII, and calcineurin-NFAT signaling. Further analyses revealed a significant increase in cross sectional area of cardiomyocytes, and in expression levels of hypertrophic markers in cultured neonatal Hspa4 KO cardiomyocytes suggesting that the hypertrophy of mutant mice was a result of primary defects in cardiomyocytes. Gene expression profile in hearts of 3.5-week-old mice revealed a differentially expressed gene sets related to ion channels and stress response. Taken together, these results reveal that HSPA4 is implicated in protection against pressure overload-induced heart failure.
Targeted disruption of Hspa4 gene leads to cardiac hypertrophy and fibrosis.
Sex
View SamplesThe heart responds to pathological overload through myocyte hypertrophy. In our study, we found that this response is regulated by cardiac fibroblasts via a novel paracrine mechanism involving plasma membrane calcium ATPase 4 (PMCA4). PMCA4 deletion in mice, both systemically and specifically in fibroblasts, reduces the hypertrophic response to pressure overload; however, knocking out PMCA4 specifically in cardiomyocytes does not produce this effect. Mechanistically, our microarray data on fibroblasts isolated from PMCA4 WT and PMCA4 knockout animals showed that cardiac fibroblasts lacking PMCA4 produce higher levels of secreted frizzled related protein 2 (sFRP2), which inhibits the hypertrophic response in neighbouring cardiomyocytes.
The plasma membrane calcium ATPase 4 signalling in cardiac fibroblasts mediates cardiomyocyte hypertrophy.
Sex, Age, Specimen part
View SamplesIn Arabidposis thaliana, the msh1 recA3 double mutant shows an extensive mitochondrial genome rearrangement and displays pronounced thermotolerance.
Extensive rearrangement of the Arabidopsis mitochondrial genome elicits cellular conditions for thermotolerance.
Specimen part
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