Genome-wide association studies (GWAS) have been pivotal to increasing our understanding of intestinal disease. However, the mode by which genetic variation results in phenotypic change remains largely unknown, with many associated polymorphisms likely to modulate gene expression. Analyses of expression quantitative trait loci (eQTL) to date indicate that as many as 50% of these are tissue specific. Here we report a comprehensive eQTL scan of intestinal tissue.
Expression quantitative trait loci analysis identifies associations between genotype and gene expression in human intestine.
Sex, Disease
View SamplesAlthough corticosteroids remain a mainstay of therapy for UC, a meta-regression of cohort studies in acute severe ulcerative colitis (UC) showed that 29% of patients fail corticosteroid therapy and require escalation of medical management or colectomy.
Gene expression changes associated with resistance to intravenous corticosteroid therapy in children with severe ulcerative colitis.
Specimen part
View SamplesPouchitis is a common complication for ulcerative colitis (UC) patients with ileal pouch-anal anastomosis (IPAA) surgery. Similarly to IBD, both innate host factors such as genetics, and environmental stimuli including the tissue-associated microbiome have been implicated in the pathogenesis. In this study, we make use of the IPAA model of inflammatory bowel disease (IBD) to carry out a study associating mucosal host gene expression with the microbiome and corresponding clinical outcomes.
Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease.
Sex, Disease, Subject
View SamplesAn efficient innate immune recognition of the intracellular parasite T. cruzi is crucial for host protection against development of Chagas disease, which often leads to multiple organ damage, particularly the heart leading to cardiomyopathy. Mechanisms modulated by MyD88 have been shown to be necessary for resistance against T, cruzi infection. Recently, Nod-like receptors have been shown to play an important role as innate immune sensors, particularly as they relate to inflammasome function, caspase activation, and inflammatory cytokine production. In this study, we aimed to investigate the participation of innate immune responses in general, and inflammasomes in particular, in heart inflammation and cardiac damage upon infection with the T. cruzi parasite.
Apoptosis-associated speck-like protein containing a caspase recruitment domain inflammasomes mediate IL-1β response and host resistance to Trypanosoma cruzi infection.
Specimen part
View SamplesWe have investigated the effect of RRP6 depletion on the transcriptome of S2 cells using Illumina deep RNA sequencing. We have also carried out Illumina ChIP-seq analysis of RRP6 genome occupancy in control S2 cells (GFP-KD) and in cells depleted of SU(VAR)3-9. Overall design: 8 samples total; 4 RNA-Seq samples (1 RRP6-KD and 1 GFP-KD, 2 biological replicates each); and 4 ChIP-Seq samples (RRP6 IP in GFP-KD and in Su(var)3-9-KD conditions; plus their respective Input samples).
An Interaction between RRP6 and SU(VAR)3-9 Targets RRP6 to Heterochromatin and Contributes to Heterochromatin Maintenance in Drosophila melanogaster.
Subject
View SamplesCD8+ T-cells inhibit virus replication in SIV-infected rhesus macaques (RM). However, it is unclear to what extent the viral suppression mediated by CD8+ T-cells reflects direct killing of infected cells as opposed to indirect, non-cytolytic mechanisms. In this study, we used functional genomics to investigate potential mechanisms of in vivo viral suppression mediated by CD8+ lymphocytes. Eight chronically SIVmac239-infected RMs underwent CD8+ lymphocyte depletion, and RNA from whole blood was obtained prior to depletion, at the nadir of CD8+ lymphocytes (5 days post-depletion), and during the repopulation phase (11 days post-depletion). Principal components analysis demonstrated that overall gene expression during the nadir of CD8+ T-cells was highly divergent from other intervals. Conversely, the genomic signature of samples from the CD8+ cell rebound phase was similar to that of pre-depletion samples. During CD8+ lymphocyte depletion we detected a strongly significant decrease in the expression of the genes encoding CD8 and CD8 chains, consistent with the near complete CD8+ T-cell depletion measured by flow cytometry. Of note, we observed significant down-regulation of the expression of genes encoding for factors that can suppress SIV replication, including the CCR5-binding chemokine CCL5/Rantes, several retroviral restriction factors (TRIM10, TRIM15, APOBEC3G/H) and defensins. Reduced expression of various genes related to T cell activation and proliferation was also observed. Collectively, these data indicate that depletion of CD8+ lymphocytes in SIV-infected RMs is associated with the establishment of a pattern of gene expression that may result in increased intrinsic permissivity to virus replication.
Transcriptional profiling of experimental CD8(+) lymphocyte depletion in rhesus macaques infected with simian immunodeficiency virus SIVmac239.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression.
Specimen part
View SamplesAnlaysis of the differential gene expression between T47D cells expressing wild type (WT) progesterone receptor isoform B (PR) or SUMOylation-deficient PR molecules.
Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression.
Specimen part
View SamplesDuplicated genes escape gene loss by conferring a dosage benefit or evolving diverged functions. The yeast Saccharomyces cerevisiae contains many duplicated genes encoding ribosomal proteins. Prior studies have suggested that these duplicated proteins are functionally redundant and affect cellular processes in proportion to their expression. In contrast, through studies of ASH1 mRNA in yeast, we demonstrate paralog-specific requirements for the translation of localized mRNAs. Intriguingly, these paralog-specific effects are limited to a distinct subset of duplicated ribosomal proteins. Moreover, transcriptional and phenotypic profiling of cells lacking specific ribosomal proteins reveals differences between the functional roles of ribosomal protein paralogs that extend beyond effects on mRNA localization. Finally, we show that ribosomal protein paralogs exhibit differential requirements for assembly and localization. Together, our data indicate complex specialization of ribosomal proteins for specific cellular processes, and support the existence of a ribosomal code.
Functional specificity among ribosomal proteins regulates gene expression.
No sample metadata fields
View SamplesCells respond heterogeneously to DNA damage. We engineered genetic circuits to detect differential responses in a population that persist for many days post-stimulus.
Synthetic memory circuits for tracking human cell fate.
Specimen part, Cell line, Treatment
View Samples