Proteomics of ACF as they mature and transform into intestinal adenomas
Ontology highlight
ABSTRACT: Proteomics of ACF as they mature and transform into intestinal adenomas in an AOM murine model consuming a normal diet under normal conditions.
Project description:Transcription profiling of normal and tumorigenic Rattus norvegicus cell lines grown under normal and arginine deprivation conditions
Project description:Organoids have the potential to bridge 3D cell culture to tissue physiology by providing a model resembling in vivo organs. We propose here a SILAC method to measure protein expression changes in intestinal organoids under different experimental conditions. With the combined use of quantitative mass spectrometry, SILAC and organoid culture, we validated the approach and showed that large-scale proteome variations can be measured in an “organ-like” system under variable conditions.
Project description:This study uses whole-genome bisulfite sequencing to characterize the methylomes of the AOM/DSS mouse model at single-base resolution. In this model, mice are treated with dextran sodium sulfate (DSS) to induce colitis. When this treatment is preceded by injections of the weak carcinogen azoxymethane (AOM) the mice develop intestinal tumors. Our results identify hypermethylated DMVs as a prominent feature of the colitis methylome that is conserved in intestinal adenocarcinomas. Further analyses reveal a subset of DMV-associated genes, expressed in normal intestinal epithelial cells, that were silenced and hypermethylated in inflamed and cancerous intestinal cells. Together, these findings provide strong support for the hypothesis that inflammatory signals induce a higher risk for cancer development by manipulating the epigenome. . Whole genome methylation analysis of M. musculus. Three conditions were sequenced analyzed, the first is an untreated control, the second corresponds to inflammation, the third to cancer induced by inflammation. All three conditions were analyzed using three replicates.
Project description:Conducted serum untargeted metabolomics analysis in AMP-activated protein kinase (AMPK) intestinal KO mice and control mice under high-fat diet (HFD) conditions
Project description:In our study, we investigated the effect of Vasoactive intestinal peptide (VIP) on murine intestinal stem cell (ISC) activity and differentiation in homeostatic conditions and following irradiation-induced injury. We utilized a model of murine intestinal organoids and observed that VIP promotes epithelial differentiation towards a secretory phenotype predominantly via the p38 MAPK pathway. Moreover, VIP prominently modulates epithelial proliferation as well as the number and proliferative activity of Lgr5-EGFP+ ISC under homeostatic conditions. Further analysis revealed that in vitro acute irradiation injury renders Lgr5-EGFP+ ISC even more susceptible to modulations by VIP, which results in the strong promotion of epithelial regeneration by VIP. Finally, these effects by VIP translate into an in vivo model of abdominal irradiation, where VIP was shown to prominently mitigate radiation-induced injury. Taken together, our findings indicate a prominent role of VIP in modulating ISC behavior in intestinal homeostasis and its potential to promote intestinal regeneration following acute irradiation injury.