Significant recent progress has been made with understanding eosinophilic gastrointestinal disorders (EGIDs) yet most studies have focused on eosinophilic esophagitis (EoE). Herein, we aimed to provide fundamental information about the molecular characteristics of eosinophilic gastritis (EG).
Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome.
Specimen part, Disease, Disease stage
View SamplesThe study tests the hypothesis that maternal mRNA translation in oocytes is sensitive to the environment in which the oocytes mature. Amphiregulin (AREG) is a critical signal for oocyte maturation but also for oocyte developmental competence. Here we have used a genome-wide approach to determine whether the oocyte translational program is affected when oocytes mature in vivo in the absence of AREG.
Somatic cells regulate maternal mRNA translation and developmental competence of mouse oocytes.
Specimen part
View SamplesThe emergence of fully antimicrobial resistant Neisseria gonorrhoeae has led global public health agencies to identify a critical need for next generation anti-gonococcal pharmaceuticals. The development and success of these compounds will rely upon valid pre-clinical models of gonorrhoeae infection. We recently developed and reported the first model of upper genital tract gonococcal infection. During initial characterization, we observed significant reproductive cycle-based variation in infection outcome. When uterine infection occurred in the diestrus phase, there was significantly greater pathology than during estrus phase. The aim of this study was to evaluate transcriptional profiles of infected uterine tissue from mice in either estrus or diestrus phase in order to elucidate possible mechanisms for these differences. Genes and biological pathways with phase-independent induction during infection showed a chemokine dominant cytokine response to Neisseria gonorrhoeae. Despite general induction being phase-independent, this common anti-gonococcal response demonstrated greater induction during diestrus phase infection. Greater activity of granulocyte adhesion and diapedesis regulators during diestrus infection, particularly in chemokines and diapedesis regulators, was also shown. In addition to a greater induction of the common anti-gonococcal response, Gene Set Enrichment Analysis (GSEA) identified a diestrus-specific induction of type-1 interferon signaling pathways. This transcriptional analysis of murine uterine gonococcal infection during distinct points in the natural reproductive cycle provided evidence for a common anti-gonococcal response characterized by significant induction of granulocyte chemokine expression and high proinflammatory mediators. The basic biology of this host response to N. gonorrhoeae in estrus and diestrus is similar at the pathway level, but varies drastically in magnitude. Overlaying this, we observed type-1 interferon induction specifically in diestrus infection where greater pathology is observed. This supports recent work suggesting this pathway has a significant, possibly host-detrimental, function in gonococcal infection. Together these findings lay the groundwork for further examination of the role of interferons in gonococcal infection. Additionally, this work enables the implementation of the diestrus uterine infection model using the newly characterized host response as a marker of pathology and its prevention as a correlate of candidate vaccine efficacy and ability to protect against the devastating consequences of N. gonorrhoeae-associated sequelae.
Murine host response to Neisseria gonorrhoeae upper genital tract infection reveals a common transcriptional signature, plus distinct inflammatory responses that vary between reproductive cycle phases.
Specimen part, Treatment
View SamplesCellular dormancy and heterogeneous cell cycle lengths provide important explanations for treatment failure following adjuvant therapy with S-phase cytotoxics in colorectal cancer (CRC) yet the molecular control of the dormant versus cycling state remains unknown. In CRCs dormant cells are found to be highly clonogenic and resistant to chemotherapies. We sought to understand the molecular features of dormant CRC cells to facilitate rationale identification of compounds to target both dormant and cycling tumour cells. Overall design: Six colorectal cancer cell lines (DLD1, HCT15, HT55, SW948, RKO and SW48) were labelled with the cell permeable dye CFSE and then grown in non-adherent spheroid culture for 6 days to enable identification of dormant cells that retain CFSE (LRC) and cycling cells (BULK). LRCs and BULK populations were then FACS sorted from each cell line in quadruplicate. As a control experiment, to identify off-target effects of the CFSE dye and culture artefacts, BULK populations from DLD1 cells at d1 and d6 after seeding both with and without CFSE labelling were included in the RNAseq analysis. RNA was extracted using the RNAeasy Micro Plus kit (Qiagen) and quantified using the Qubit RNA Assay Kit (Thermo Fisher Scientific). RNA quality was assessed using the Agilent Bioanalyser system as per manufacturer's instructions. Following normalisation and sample randomisation, Truseq library (Illumina) preparation was carried out at the CRUK CI genomics facility and subsequent single end, 50bp sequencing using the HiSeq system (Illumina). Following human genome alignment (hg19), read counts were normalised and differential expression tested using the DEseq protocol.
Itraconazole targets cell cycle heterogeneity in colorectal cancer.
Specimen part, Cell line, Subject
View SamplesTwo cell lines (HT55 and SW948) were found responsive to itraconazole treatment. To identify the mode of action cells were treated with itraconazole or control (DMSO) and then subjected to RNAseq analysis once the phenotype had developed Overall design: HT55 and SW948 cells were seeded in adherent culture and treated with 5uM itraconazole or DMSO for 6 days. Cells then underwent RNA extraction using the RNAeasy Micro Plus kit (Qiagen) and quantified using the Qubit RNA Assay Kit (Thermo Fisher Scientific). RNA quality was assessed using the Agilent Bioanalyser system as per manufacturer's instructions. Following normalisation and sample randomisation, Truseq library (Illumina) preparation was carried out at the CRUK CI genomics facility and subsequent single end, 50bp sequencing using the HiSeq system (Illumina). Following human genome alignment (hg19), read counts were normalised and differential expression tested using the DEseq protocol.
Itraconazole targets cell cycle heterogeneity in colorectal cancer.
Specimen part, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Rapamycin response in tumorigenic and non-tumorigenic hepatic cell lines.
No sample metadata fields
View SamplesTwo rat hepatic cell lines, WB-F344 and WB311, were characterized for the effect of rapamycin on gene expression. The WB311 cell line, which is tumorigenic and resistant to the growth inhibitory effects of rapamycin, was originally derived from the WB-F344 parental hepatic epithelial cell line. The goal of this experiment was to identify genes that responded to rapamycin in the sensitive cells but not the resistant cells, thereby providing insight into the mechanism of rapamycin resistance.
Rapamycin response in tumorigenic and non-tumorigenic hepatic cell lines.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1.
Specimen part, Cell line, Treatment
View SamplesHuman HOS cell line was differentiated by beta-glycerophosphate (BGP) treatment and gene expression profiling was studied with Illumina expression microarray (HumanHT12_V4).
miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1.
Specimen part, Cell line, Treatment
View SamplesHuman HOS cell line was overexpressed with miR23a and gene expression profiling was studied with Illumina expression microarray (HumanHT12_V4).
miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1.
Specimen part, Cell line
View Samples