This SuperSeries is composed of the SubSeries listed below.
Genome-wide identification of expression quantitative trait loci (eQTLs) in human heart.
Sex, Age, Specimen part
View SamplesIn recent years genome-wide association studies (GWAS) have uncovered numerous chromosomal loci associated with various electrocardiographic traits and cardiac arrhythmia predisposition. A considerable fraction of these loci lie within inter-genic regions. Trait-associated SNPs located in putative regulatory regions likely exert their effect by modulating gene expression. Hence, the key to unraveling the molecular mechanisms underlying cardiac traits is to interrogate variants for association with differential transcript abundance by expression quantitative trait locus (eQTL) analysis. In this study we conducted an eQTL analysis of human heart. To this end, left ventricular mycardium samples from non-diseased human donor hearts were hybridized to Illumina HumanOmniExpress BeadChips for genotyping (n = 129) and Illumina Human HT12 Version 4 BeadChips (n = 129) for transcription profiling.
Genome-wide identification of expression quantitative trait loci (eQTLs) in human heart.
Sex, Age, Specimen part
View SamplesThe intact intestinal epithelial barrier protects our body from a range of immune mediated diseases. The epithelial layer has an impressive ability to reconstitute and repair upon damage and this process of repair is increasingly seen as a therapeutic target. In vitro models to study this process in primary intestinal cells are lacking. Therefore we established and characterized an in vitro model of intestinal damage and repair by applying γ-radiation on small intestinal organoids. We then used this model to identify novel regulators of intestinal regeneration.
No associated publication
Specimen part, Time
View SamplesResponse to allergen was studied in epithelial cells derived from allergic pantients and from healthy controls. Cells were cultured after isolation from a nasal biopsy. Cells were exposed to Housed dust mite or vessel (saline)
Primary nasal epithelium exposed to house dust mite extract shows activated expression in allergic individuals.
No sample metadata fields
View SamplesIn colorectal cancer, the role of the most common driver mutations in APC, KRAS, SMAD4 and TP53, on global mRNA translation are incompletely understood. To adress this, we generated and characterised mouse intestinal organoid models with oncogenic mutations in each of these genes using Cre-Lox recombination in ex vivo organoid cultures combined with stable expression of short hairpin RNAs. Microarray analysis was used to characterise transcriptomic reprogramming that supports altered global translation rates in mutant cells.
No associated publication
Specimen part
View SamplesAP1 transcription factor family members: activating transcription factor 2 (ATF2) and activating transcription factor 7 (ATF7) have highly redundant functions due to homology and hence overlapping DNA-binding sites. The role of these transcription factors in intestinal epithelial homeostasis and repair has not been critically examined. Here, by using an intestine-specific deletion of ATF2 combined with body wide deletion of ATF7 in mice we assess the role of these proteins during intestinal homeostasis and repair after inflammation.
No associated publication
Specimen part, Treatment
View SamplesThis experiment was performed to assess the effect of loss of Hnf4a in the intestinal epithelium on the regeneration process after irradiation. Intestinal epithelium specific knockout was obtained by oral adminstration of tamoxifen to VillinCreERT2+-Hnf4afl/fl mice and VillinCreERT2--Hnf4afl/fl mice (which served as controls). 3 weeks after the tamoxifen administration, mice received 14 Gy whole-body gamma-irradiation. RNA was extracted from small intestinal tissue 96 hours after irradiation.
No associated publication
Specimen part, Time
View SamplessiRNA mediated gene knockdown has been shown to be extremely sequence specific. However, off-target gene regulation due to partial sequence homology has also been reported. Furthermore, sequence unrelated effects on gene regulation can occur when siRNA is applied in vivo. In this experiment we investigated off target gene regulation due to treatment of mice with siRNA and LNA modified siRNA targeting GFP. Off target gene regulation was observed and was markedly reduced upon introduction of LNA modifiecation in siRNA.
No associated publication
No sample metadata fields
View SamplesThe functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34- negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis.
CD34 marks angiogenic tip cells in human vascular endothelial cell cultures.
Specimen part, Subject
View SamplesResponse to allergen was studied in bronchial epithelial cell line H292. Cells were cultured and subsequently exposed to House dust mite or vessel (saline)
Allergen induced gene expression of airway epithelial cells shows a possible role for TNF-alpha.
No sample metadata fields
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