Data Set Group2: EPFL/LISP BXD CD+HFD Gastrointestinal Affy Clariom S GeneLevel Main (Sep17) RMA

Data Set: EPFL/LISP BXD CD+HFD Gastrointestinal Affy Clariom S GeneLevel Main (Sep17) RMA GN Accession: GN839 GEO Series: GSE225791 Title: Genetic and dietary modulators of the inflammatory response in the gastro-intestinal tract of the BXD mouse genetic reference population Organism: Mouse (Mus musculus, mm10) Group: BXD Tissue: Gastrointestinal mRNA Dataset Status: Private Platforms: Affymetrix Clariom S Array Mouse Normalization: RMA

Contact Information Johan Auwerx Ecole Polytechnique Federale de Lausanne Bâtiment AI, Chambre 1351 Lausanne, Lausanne 1015 Switzerland Tel. +41 216930951 admin.auwerx@epfl.ch Website Download datasets and supplementary data files

Specifics of this Data Set:

CD + HFD

Summary:

Inflammatory gut disorders, including inflammatory bowel disease (IBD), can be impacted by dietary, environmental and genetic factors. While the incidence of IBD is increasing worldwide, we still lack a complete understanding of the gene-by-environment interactions underlying inflammation and IBD. Here, we profiled the colon transcriptome of 52 BXD mouse strains fed with a chow or high-fat diet (HFD) and identified a subset of BXD strains that exhibit an IBD-like transcriptome signature on HFD, indicating that an interplay of genetics and diet can significantly affect intestinal inflammation. Using gene co-expression analyses, we identified modules that are enriched for IBD-dysregulated genes and found that these IBD-related modules share cis-regulatory elements that are responsive to the STAT2, SMAD3, and REL transcription factors. We used module quantitative trait locus (ModQTL) analyses to identify genetic loci associated with the expression of these modules. Through a prioritization scheme involving systems genetics in the mouse and integration with external human datasets, we identified Muc4 and Epha6 as the top candidates mediating differences in HFD-driven intestinal inflammation. This work provides insights into the contribution of genetics and diet to IBD risk and identifies two candidate genes, MUC4 and EPHA6, that may mediate IBD susceptibility in humans. https://elifesciences.org/reviewed-preprints/87569

About the cases used to generate this set of data:

About the tissue used to generate this set of data:

About the array platform:

About data values and data processing:

Notes:

Experiment Type:

At 29 weeks of age, mice of 52 BXD strains including parental C57BL/6J and DBA/2J strains were fasted overday and then were sacrificed. Phenotyping were performed and multi-organ were flash-frozen and bio-banked for future use, the assoiacted datasets are mentioned in the paper. In this study, proximal colon samples were collected and immediately frozen in liquid nitrogen for RNA extraction and RNEasy cleanup. Each dietary and strain cohort consisted of ~5 animals which were prepared independently then pooled evenly by µg RNA before the Affymetrix arrays were run.

Contributor:

Auwerx J, Li X, Bachmann A, Rapin A, Sleiman MB, Morel J

Citation:

Li X, Morel JD, Benegiamo G, Poisson J et al. Genetic and dietary modulators of the inflammatory response in the gastrointestinal tract of the BXD mouse genetic reference population. Elife 2023 Oct 19;12. PMID: 37855835

Data source acknowledgment:

Study Id:

268

• The UT Center for Integrative and Translational Genomics
• NIGMS Systems Genetics and Precision Medicine project (R01 GM123489, 2017-2021)
• NIDA NIDA Core Center of Excellence in Transcriptomics, Systems Genetics, and the Addictome (P30 DA044223, 2017-2022)
• NIA Translational Systems Genetics of Mitochondria, Metabolism, and Aging (R01AG043930, 2013-2018)
• NIAAA Integrative Neuroscience Initiative on Alcoholism (U01 AA016662, U01 AA013499, U24 AA013513, U01 AA014425, 2006-2017)
• NIDA, NIMH, and NIAAA (P20-DA 21131, 2001-2012)
• NCI MMHCC (U01CA105417), NCRR, BIRN, (U24 RR021760)