Genomic profile of IL10-/- knocked out colitis model
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE9297 | GEO | 2008/11/01
SECONDARY ACCESSION(S): PRJNA102941
REPOSITORIES: GEO
Similar Datasets
Project description:Objetives: study and characterization of the IL10-/- knocked out colitis model in mice at genomic level and the study of the influence of bacteria in the development of the disease. Experiment Overall Design: We used three groups of animasl: 1)IL10-/- mice grown under conventional condition, 2)IL10-/- mice grown under specific pathogen free (SPF) conditions, 3) Wild type mice grown under conventional conditions (CONTROL group). For each group, we recovered samples at 7, 9 and 12 weeks after birth According to colon length and colonic damage, three replicates were selected for each time point and each group (27 samples), for genomic analysis. Experiment Overall Design: RNA was extracted from homogenized full-thickness colonic tissues in Trizol® reagent (Invitrogen) and purified with RNeasy affinity columns (Qiagen), according to manufacturer´s protocol. The microarray analysis was performed by Progenika Biopharma (Bilbao, Spain) on GeneChip® Rat Genome 230 2.0 Array (Affymetrix). All sample labeling (biotin), hybridization, staining and scanning procedures were carried out using Affimetrix, standard protocols (www.affymetrix.com). Normalization was carried out using Bioconductor sofware (affyPLM package).
2008-11-13 | E-GEOD-9297 | biostudies-arrayexpress
Project description:The loss of TNFR1 (Tnfrsf1a) in the Il10-/- spontaneous mouse colitis background results in acceleration of disease onset. Whereas Il10-/- mice on the Bl/6 background are relatively protected from colitis throughout life, Il10-/- Tnfr1-/- mice develop colitis beginning at 4 wks of age. Their disease results in nearly 50% mortality by 12 wks of age. We hypothesized that this early-onset colitis was due to dysregulation of immune signals in early life, defining a key period known as the "weaning reaction" in which proinflammatory signals help induce mucosal tolerance of the microbiome. To test this hypothesis, we profiled, using mRNA-Seq, the colonic transcriptomes from Il10-/- and Il10-/- Tnfr1-/- mice at 2 wks of age. The results presented here show that Il10-/- Tnfr1-/- mice have reduced expression of cytokines at this early age, suggesting that they cannot amount an appropriate immune response. Thus, TNFR1 plays an important role in the weaning reaction and the acquisition of tolerance.
2020-08-04 | GSE155626 | GEO
Project description:That commensal bacteria can influence intestinal inflammation has been observed using other models of chronic colitis. Loss of IL-10, a major immunosuppressive cytokine, induces spontaneous colitis in mice. The incidence of spontaneous polyp formation in IL-10-deficient mice was also completely eliminated in the absence of STING We used microarrays to evaluate the inflammatory cytokine expression in the colon from IL10 KO mice and IL10/STING KO mice.
2018-02-01 | GSE107810 | GEO
Project description:Lcn2 is involved in host defense against pathogens, but the function in intestinal mucosal immunity and inflammation remains largely unknown. Genetic ablation of Lcn2 results in early-onset colitis and spontaneous emergence of right-sided colonic tumors in the setting of IL-10 deficiency (Lcn2-/-;IL10-/- mice). To address whether inflammation or other mechanisms drives the site-specific tumor locations gene expression analyses in proximal versus distal colons of Lcn2-/- IL10-/- mice were performed. Differential expression between distal colon versus cecum and proximal colon samples were analyses using Affymetrix MoGene 2.0 ST arrays on formalin-fixed, paraffin-embedded tissue sections of Lcn2-/-; IL10-/-mice.
2016-03-30 | E-MTAB-4583 | biostudies-arrayexpress
Project description:Effects of TNFR1 deletion on Il10-/- mouse colitis in early life
| PRJNA650513 | ENA
Project description:Genomic profile of IL10-/- knocked out colitis model
| PRJNA102941 | ENA
Project description:The aim of this study is to compare the transcriptomic profile of colonic intestinal epithelial cells (IECs) at steady-state, and in several models of colitis: in naive wild-type C57BL/6 mice, in wild-type C57BL/6 mice treated for 7 days with 3% dextran sodium sulfate (DSS) in drinking water, in Il10-/- C57BL/6 mice and Il10-/- C57BL/6 mice with IEC-specific Rabgef1 deletion. Colonic IECs were isolated and FACS-sorted, then subjected tu bulk RNA-seq.
2019-09-30 | E-MTAB-7315 | biostudies-arrayexpress
Project description:Ulcerative Colitis fecal samples were transplanted into IL10 deficient gnotobiotic mice. Half of the mice received a protease inhibitor cocktail in their drinking water. After 8-weeks colonization the animals were studied for colonic inflammation, and fecal samples were collected and analyzed by LC-MS3 based quantitative metaproteomics. Data from mice transplanted with two UC patients were analyzed in this dataset.
2020-11-23 | MSV000086510 | MassIVE
Project description:IL-27 is an immunoregulatory cytokine that suppresses inflammation through multiple mechanisms including induction of IL-10, but the transcriptional network mediating its diverse functions remains unclear. Combining temporal RNA profiling with computational algorithms, we predict 79 transcription factors induced by IL-27 in T cells. We validate 11 known and discover 5 positive (Cebpb, Fosl2, Tbx21, Hlx, Atf3) and 2 negative (Irf9, Irf8) Il10 regulators, generating an experimentally refined regulatory network for Il10. We report two central regulators Prdm1 and Maf that cooperatively drive the expression of signature genes induced by IL-27 in Type 1 regulatory T cells, mediate IL-10 expression in all T helper cells, and determine the regulatory phenotype of colonic Foxp3+regulatory T cells. Prdm1/Maf double-knockout mice develop spontaneous colitis, phenocopying the ll10 deficient mice. Our work provides insights for IL-27 driven transcriptional networks and identifies two shared Il10 regulators that orchestrate immunoregulatory programs across T helper cell subsets.
2020-12-21 | GSE158703 | GEO
Project 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. Material & Methods: Two independent microarray experiments were performed using SPF mice: 19 for the first experiment (4 C3 WT [GSM39296], 5 C3-Il10-/- [GSM39297], 5 B6 WT [GSM39290], 5 B6-Il10-/- [GSM39291]) and 18 for the second (4 C3 WT [GSM39295], 4 C3-Il10-/- [GSM39294], 5 B6 WT [GSM39288], 5 B6-Il10-/- [GSM39289]). The mice were euthanized by cervical dislocation. Following a ventral midline incision, the colon (including the rectum, but not the anus) was removed and flushed with PBS. Each colon was opened longitudinally with a pair of scissors, further dissected and homogenized using a micropistill in 1.5 ml peqGOLD Trifast FL. RNA was isolated according to the manufacturer´s protocol, and quality was checked using RNA Nano LabChip® technology (Agilent, Böblingen, Germany). For each of the two array experiments, equal amounts (7 micro gram) of RNA were pooled from the four or five animals of each mouse strain, resulting in a total of eight samples. For biotin-labeled target synthesis starting from 3-5 µg of total RNA, reactions were performed using standard protocols supplied by the manufacturer (Affymetrix; Santa Clara, CA). Briefly, 3-5 µg total RNA were converted to dsDNA using 100 pmol of a T7T23V primer (Eurogentec; Seraing, Belgium) containing a T7 promoter. The cDNA was then used directly in an in-vitro transcription reaction in the presence of biotinylated nucleotides. The concentration of biotin-labeled cRNA was determined by UV absorbance. In all cases, 12.5 µg of each biotinylated cRNA preparation were fragmented and placed in a hybridization cocktail containing four biotinylated hybridization controls (BioB, BioC, BioD, and Cre) as recommended by the manufacturer. Samples were hybridized to an identical lot of Affymetrix MG U74Av2 for 16 hours. Data selection and transformation procedures. For normalization, all array experiments were scaled to a target intensity of 150, otherwise using the default values of the Microarray suite 5.0 (MAS 5.0). Filtering of the results was done as follows: Genes were considered as strong regulated if their fold change was greater than or equal 2 or less than or equal -2, the statistical parameter for a significant change was less than 0.01 (change p-Value for changes called Increased) or greater than 0.99 (change p-Value for changes called Decreased). Additionally, the signal difference of a certain gene was greater than 200. Genes were considered as weak regulated if their fold change was greater than or equal 1.5 or less than or equal -1.5, the statistical parameter for a significant change was less than 0.001 or greater than 0.999 and the signal difference of a certain gene was greater than 40. Keywords = Inflammatory Bowel Disease Keywords = IBD Keywords = interleukin-10 Keywords = microarray Keywords = mice Keywords = quantitative trait locus Keywords = QTL Keywords = susceptibility Keywords: parallel sample
2005-12-31 | GSE2172 | GEO