Background and aims. The etiopathology of inflammatory bowel diseases is still poorly understood. To date, only few little data are available on the microbiota composition in ulcerative colitis (UC), representing a major subform of inflammatory bowel diseases. Currently, one of the main challenges is to unravel the interactions between genetics and environmental factors in the onset or during the progression and maintenance of the disease. The aim of the present study was to analyse twin pairs discordant for UC for both gut microbiota dysbiosis and host expression profiles at a mucosal level and to get insight into the functional genomic crosstalk between microbiota and mucosal epithelium in vivo. Methods. Biopsies were sampled from the sigmoid colon of both healthy and diseased siblings from UC discordant twin pairs but also from healthy twins. Microbiota profiles were assessed by 16S rDNA libraries while mRNA expression profiles were analysed from the same volunteers using Affymetrix microarrays.
Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis.
Specimen part, Subject
View SamplesWhole genome expression profiling of 40 healthy human twins (20 monozygotic, 20 dizygotic)
Genetic control of global gene expression levels in the intestinal mucosa: a human twin study.
Sex, Age
View SamplesSlow-cycling subpopulations exist in bacteria, yeast, and mammalian systems. In the case of cancer, slow-cycling subpopulations have been proposed to give rise to drug resistance. However, the origin of slow-cycling human cells is poorly studied, in large part due to lack of markers to identify these rare cells. Slow-cycling cells pass through a non-cycling period marked by low CDK2 activity and high p21 levels. Here, we use this knowledge to isolate these naturally slow-cycling cells from a heterogeneous population and perform RNA-sequencing to delineate the transcriptome underlying the slow-cycling state. We show that cellular stress responses – the p53 transcriptional response and the integrated stress response – are the most salient causes of spontaneous entry into the slow-cycling state. Overall design: mRNA profiling of spontaneously quiescent human cells and cells forced into quiescence by four different methods
Spontaneously slow-cycling subpopulations of human cells originate from activation of stress-response pathways.
Cell line, Subject
View SamplesLaser capture microdissection coupled with microarray genes expression analysis were utilized in order to elucidate the regulatory networks active in epithelial cells of the neonatal and adult mouse uterus.
Cell-specific transcriptional profiling reveals candidate mechanisms regulating development and function of uterine epithelia in mice.
Specimen part
View SamplesTo identify genes differentially expressed in the glandless uterus, whole uteri were collected from control (uterine glands present) and PUGKO (no uterine glands) mice at day of pseudopregnancy (DOPP) 3.5 (day DOPP 0.5= vaginal plug). Microarray analysis identified differentially expressed genes in the glandless uteri of PUGKO mice as compared to control mice.
Cell-specific transcriptional profiling reveals candidate mechanisms regulating development and function of uterine epithelia in mice.
Specimen part
View SamplesTranscriptional analysis of the effects of the deletion of the sRNAs glmY and glmZ in EHEC
Global analysis of posttranscriptional regulation by GlmY and GlmZ in enterohemorrhagic Escherichia coli O157:H7.
No sample metadata fields
View SamplesGene expression analysis has been established as a tool for the characterization of genotoxic mechanisms of chemical mutagens. This approach has been shown to differentiate between DNA reactive genotoxins and non-DNA reactive or indirectly-acting genotoxins. In this context, it has been suggested that expression analysis is capable of distinguishing compounds that cause DNA damage from those that interfere with mitotic spindle function. Formaldehyde (FA) is known to be a DNA-reactive substance which mainly induces chromosomal damage in cultured mammalian cells. However, there has been concern that FA might also act as an aneugen (i.e., induce aneuploidy) but recent cytogenetic studies did not support this assumption. To further characterize FA's genotoxic mode of action, we now used gene expression profiling as a molecular tool to differentiate between clastogenic and aneugenic activity. TK6 cells were exposed to FA for 4 and 24 h and changes in gene expression were analyzed using a whole-genome human microarray. Results were compared to the expression profiles of two DNA-damaging clastogens (methyl methanesulfonate [MMS] and ethyl methanesulfonate [EMS]) and two aneugens (colcemid [COL] and vincristine [VCR]). The gene expression profiles indicated that clastogens and aneugens induce discriminable gene expression patterns. The expression profile of FA showed more similarities to clastogens than to aneugens. Hierarchical clustering analysis as well as several class prediction algorithms revealed a much closer relationship of FA with clastogens than with aneugens. A pathway analysis of differentially regulated genes also demonstrated an overall better agreement of FA with clastogens than with aneugens. Altogether, the results of this study revealed great similarities in gene expression in response to FA and clastogens but did not support an aneugenic activity of FA.
Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells.
Cell line, Treatment
View SamplesUsing various exposure conditions, we studied the induction of DNA-protein crosslinks (DPX) by formaldehyde (FA) and their removal in primary human nasal epithelial cells (HNEC). DPX were indirectly measured by the alkaline comet assay as the reduction of gamma ray induced DNA migration. DPX are the most relevant primary DNA alterations induced by FA and the comet assay is a very sensitive method for the detection of FA-induced DPX. In parallel experiments, we investigated changes in gene expression by using a full genome human microarray. After a single treatment with FA (50 to 200 M), concentration and time-dependent changes in gene expression were seen under conditions that also induced genotoxicity. Repeated treatments with low FA concentrations (20 and 50 M) did not lead to a significant induction of DPX but repeated treatments with 50 M FA changed the expression of more than 100 genes. Interestingly, the expression of genes involved in the main pathway for FA detoxification and the repair of DPX were not specifically enhanced. A high degree of overlap was seen among the pattern of gene changes induced by FA in HNEC in comparison to recently published array studies for nasal epithelial cells from rats exposed to FA in vivo. Our results suggest that HNEC are a suited in vitro model for the characterization of FA-induced toxicity and the relationship between genotoxic and other cytotoxic effects.
Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro.
Specimen part, Treatment
View SamplesTo identify candidate genes regulated by forkhead transcription factor box A2 (FOXA2) in the uterus, control and Foxa2-deleted uteri were collected at day of pseudopregnancy (DOPP) 3.5 (DOPP 0.5= vaginal plug). Microarray analysis identified differentially expressed genes in the Foxa2-deleted as compared to control uteri that are candidiate FOXA2-regulated genes in the uterus.
Integrated chromatin immunoprecipitation sequencing and microarray analysis identifies FOXA2 target genes in the glands of the mouse uterus.
Specimen part
View SamplesThese E. coli strains were grown with various signaling molecules and the expression profiles were determined.
Global effects of the cell-to-cell signaling molecules autoinducer-2, autoinducer-3, and epinephrine in a luxS mutant of enterohemorrhagic Escherichia coli.
No sample metadata fields
View Samples