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GSE2172
Mus musculus
8 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Abstract: Interleukin-10-deficient (Il10-/-) mice serve as a model for inflammatory bowel disease (IBD). The severity of colitis strongly depends on the inbred strain carrying the disrupted Il10 gene: C3H/HeJBir (C3) confers disease susceptibility, whereas C57BL/6J (B6) confers resistance. Genome-wide scans with microsatellite markers on segregrating backcross and F2 populations resulted in the detection of ten colitogenic quantitative trait loci (QTL). The aim of this study was to reduce the large number of candidate genes within the QTL intervals by identifying those genes which are located within the candidate gene intervals and which are differentially expressed in the colon of IBD-susceptible and -resistant strains. Using this combination of QTL mapping and microarray analysis, we identified 16 genes which were differentially expressed between B6- and C3-Il10-/- mice and were located within the candidate gene intervals. Three of these genes (Pla2g2a, Gbp1, Cd14) showed prominent differences in expression levels between B6- and C3-Il10-/- as well as between B6 and C3 wildtype mice and were considered to be major candidate genes. Pla2g2a and Gbp1 are known to be polymorphic between C3 and B6 mice. Expression data for Cd14 were confirmed by real-time RT PCR using specified pathogen free and germfree Il10-/- mice. In conclusion, the large number of candidate genes was reduced to three major candidates by using a combination of QTL mapping and microarray analysis. All three genes play an important role in inflammatory processes and immune response.
Publication Title
Cd14, Gbp1, and Pla2g2a: three major candidate genes for experimental IBD identified by combining QTL and microarray analyses.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background and Aims: In the interleukin-10-deficient (Il10-/-) mouse model of IBD, 10 quantitative trait loci (QTL) have been shown to be associated with colitis susceptibility by linkage analyses on experimental crosses of highly susceptible C3H/HeJBir (C3Bir)-Il10-/- and partially resistant C57BL/6J (B6)-Il10-/- mice. The strongest locus (C3Bir-derived cytokine deficiency-induced colitis susceptibility [Cdcs]1 on Chromosome [Chr] 3) controlled multiple colitogenic subphenotypes and contributed the vast majority to the phenotypic variance in cecum and colon. This was demonstrated by interval-specific Chr 3 congenic mice wherein defined regions of Cdcs1 from C3Bir or B6 were bred into the IL-10-deficient reciprocal background and altered the susceptible or resistant phenotype. Furthermore, this locus likely acts by inducing innate hypo- and adaptive hyperresponsiveness, associated with impaired NFB responses of macrophages. The aim of the present study was to dissect the complexity of Cdcs1 by further development and characterization of reciprocal Cdcs1 congenic strains and to identify potential candidate genes in the congenic interval. Material and Methods: In total, 15 reciprocal congenic strains were generated from Il10-/- mice of either C3H/HeJBir or C57BL/6J backgrounds by 10 cycles of backcrossing. Colitis activity was monitored by histological grading. Candidate genes were identified by fine mapping of congenic intervals, sequencing, microarray analysis and a high-throughput real-time RT-PCR approach using bone marrow-derived macrophages. Results: Within the originally identified Cdcs1-interval, three independent regions were detected that likely contain susceptibility-determining genetic factors (Cdcs1.1, Cdcs1.2, and Cdcs1.3). Combining results of candidate gene approaches revealed Fcgr1, Cnn3, Larp7, and Alpk1 as highly attractive candidate genes with polymorphisms in coding or regulatory regions and expression differences between susceptible and resistant mouse strains. Conclusions: Subcongenic analysis of the major susceptibility locus Cdcs1 on mouse chromosome 3 revealed a complex genetic structure. Candidate gene approaches revealed attractive genes within the identified regions with homologs that are located in human susceptibility regions for IBD.
Publication Title
Cdcs1 a major colitis susceptibility locus in mice; subcongenic analysis reveals genetic complexity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Claudin-16 deficiency leads to renal salt wasting in humans and mice. Analysis of renal gene expression in Claudin-16 deficient mice, compared to heterozygous and wild type littermates, was performed to gain insights into molecular mechanisms compensating salt loss. Our results indicate the upregulation of known and putative genes for renal transcellular transporters. Furthermore, we could identify a transcript so far not associated with renal salt metabolism, which will provide a first link to a human electrolyte disorder disease.
Publication Title
Targeted deletion of murine Cldn16 identifies extra- and intrarenal compensatory mechanisms of Ca2+ and Mg2+ wasting.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 70 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
GSE2240 contains two different experimental subsets:
Publication Title
Functional profiling of human atrial and ventricular gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 29 Downloadable Samples
Illumina HiSeq 2500
Description
Gut-draining mesenteric lymph nodes (mLNs) play a key role in peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment for efficient de novo induction of Foxp3+ regulatory T cells (Tregs). We recently identified mLN stromal cells as critical cellular players in this process and demonstrated that their tolerogenic properties are imprinted by microbiota. Here, we show that this imprinting process already takes place in the neonatal phase and renders the mLN stromal cell compartment resistant to inflammatory perturbations later in life. Utilizing LN transplantation, RNA-seq and single-cell RNA-seq allowed identification of stably imprinted expression signatures in mLN fibroblastic stromal cells. We dissected common stromal cell subsets across gut-draining mLNs and skin-draining LNs with location-specific immunomodulatory functions, such as subset-specific expression of Aldh1a2/3. Accordingly, mLN stromal cells shaped resident dendritic cells to attain high Treg-inducing capacity in a Bmp2-dependent manner. Thus, crosstalk between mLN stromal and resident dendritic cells provides a robust feedback mechanism for the maintenance of intestinal tolerance. Overall design: Transcriptomic analysis of fibroblastic stromal cells of skin-draining and intestinal-draining lymph nodes from endogenous and transplanted lymph nodes at the popliteal fossa.
Publication Title
Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Illumina HiSeq 2500
Description
Gut-draining mesenteric lymph nodes (mLNs) play a key role in peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment for efficient de novo induction of Foxp3+ regulatory T cells (Tregs). We recently identified mLN stromal cells as critical cellular players in this process and demonstrated that their tolerogenic properties are imprinted by microbiota. Here, we show that this imprinting process already takes place in the neonatal phase and renders the mLN stromal cell compartment resistant to inflammatory perturbations later in life. Utilizing LN transplantation, RNA-seq and single-cell RNA-seq allowed identification of stably imprinted expression signatures in mLN fibroblastic stromal cells. We dissected common stromal cell subsets across gut-draining mLNs and skin-draining LNs with location-specific immunomodulatory functions, such as subset-specific expression of Aldh1a2/3. Accordingly, mLN stromal cells shaped resident dendritic cells to attain high Treg-inducing capacity in a Bmp2-dependent manner. Thus, crosstalk between mLN stromal and resident dendritic cells provides a robust feedback mechanism for the maintenance of intestinal tolerance. Overall design: Transcriptomic analysis of resident dendritic cells of skin-draining and intestinal-draining lymph nodes from endogenous and lymph nodes transplanted to the popliteal fossa.
Publication Title
Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2500
Description
Gut-draining mesenteric lymph nodes (mLNs) play a key role in peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment for efficient de novo induction of Foxp3+ regulatory T cells (Tregs). We recently identified mLN stromal cells as critical cellular players in this process and demonstrated that their tolerogenic properties are imprinted by microbiota. Here, we show that this imprinting process already takes place in the neonatal phase and renders the mLN stromal cell compartment resistant to inflammatory perturbations later in life. Utilizing LN transplantation, RNA-seq and single-cell RNA-seq allowed identification of stably imprinted expression signatures in mLN fibroblastic stromal cells. We dissected common stromal cell subsets across gut-draining mLNs and skin-draining LNs with location-specific immunomodulatory functions, such as subset-specific expression of Aldh1a2/3. Accordingly, mLN stromal cells shaped resident dendritic cells to attain high Treg-inducing capacity in a Bmp2-dependent manner. Thus, crosstalk between mLN stromal and resident dendritic cells provides a robust feedback mechanism for the maintenance of intestinal tolerance. Overall design: Transcriptomic analysis of migratory dendritic cells of skin-draining and intestinal-draining lymph nodes from endogenous and lymph nodes transplanted to the popliteal fossa.
Publication Title
Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Large inter-individual variance has been observed in sensitivity to drugs. To comprehensively decipher the genetic contribution to these variations in drug susceptibility, we present a genome-wide model utilizing human lymphoblastoid cell lines from the International HapMap consortium, of which extensive genotypic information is available, to identify genetic variants that contribute to chemotherapeutic agent-induced cytotoxicity. Our model integrated genotype, gene expression and sensitivity of HapMap cell lines to drugs. Cell lines derived from 30 trios of European descent (CEU) and 30 trios of African descent (YRI) were utilized. Cell growth inhibition at increasing concentrations of etoposide for 72 h was determined using alamarBlue assay. Gene expression on 176 HapMap cell lines (87 CEU and 89 YRI) was determined using the Affymetrix GeneChip Human Exon 1.0ST Array. We evaluated associations between genotype and cytotoxicity, genotype and gene expression and correlated gene expression of the identified candidates with cytotoxicity. The analysis identified 63 genetic variants that contribute to etoposide-induced toxicity through their effect on gene expression. These include genes that may play a role in cancer (AGPAT2, IL1B and WNT5B) and genes not yet known to be associated with sensitivity to etoposide. This unbiased method can be used to elucidate genetic variants contributing to a wide range of cellular phenotypes induced by chemotherapeutic agents.
Publication Title
A genome-wide approach to identify genetic variants that contribute to etoposide-induced cytotoxicity.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 125 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
In addition to the differences between populations in transcriptional and translational regulation of genes, alternative pre-mRNA splicing (AS) is also likely to play an important role in regulating gene expression and generating variation in mRNA and protein isoforms. Recently, the genetic contribution to transcript isoform variation has been reported in individuals of recent European descent. We report here results of an investigation of the differences in AS patterns between human populations. AS patterns in 176 HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry were evaluated using the Affymetrix GeneChip Human Exon 1.0 ST Array. A variety of biological processes such as immune response and mRNA metabolic process were found to be enriched among the differentially spliced genes. The differentially spliced genes also include some involved in human diseases that have different prevalence or susceptibility between populations. The genetic contribution to the population differences in transcript isoform variation was then evaluated by a genome-wide association using the HapMap genotypic data on single nucleotide polymorphisms (SNPs). The results suggest that local and distant genetic variants account for a substantial fraction of the observed transcript isoform variation between human populations.
Publication Title
Identification of common genetic variants that account for transcript isoform variation between human populations.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2000
Description
We used Ribo-seq to examine the effect of Myc activation on protein translation in U2OS cells and correalted these changes with alterations in RNA level measured by RNA-seq on tye same conditions. We also examined these effects in the presence of Torin-1, an inhibitor of mTOR Overall design: We measure ribosome occupancy profiles in U2OS cells containing an inducible Myc expression vector that were induced or mock-treated in duplicates for 36 hours. In addition, we repeated the experiments in the presence of Torin-1, an inhibitor of mTOR.
Publication Title
Myc coordinates transcription and translation to enhance transformation and suppress invasiveness.
Sample Metadata Fields
No sample metadata fields
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