Dataset Information

Multi-omic spatial atlas shows Deleted inMalignantBrain Tumours 1 (DMBT1) glycoprotein is lost in colonic dysplasia I

ABSTRACT: Colorectal cancer(CRC) is responsible for 50,000 deaths annually in the United States. Emerging evidence supports a causal role for pro-carcinogenic bacteria in the colonic microbiome. We previously showed toxigenic C. difficile from human CRC-associated bacterial biofilms accelerates tumourigenesis in ApcMin/+ mice, both in specific pathogen-free mice and in gnotobiotic mice colonised with a defined consortium of bacteria. To further understand host-microbe interactions during colonic tumourigenesis, we combined single-cell RNA-sequencing (scRNA-seq), spatial transcriptomics, and immunofluorescence to define the molecular spatial organization of colonic dysplasia in our consortium model with or without C. difficile. Our data show a striking bipartite regulation of Deleted in Malignant Brain Tumours 1 (DMBT1) in the inflamed versus dysplastic colon. From scRNA-seq, differential gene expression analysis of normal absorptive colonocytes at 2 weeks post-inoculation showed DMBT1 upregulated by C. difficile compared to colonocytes from mice without C. difficile exposure. In contrast, our spatial transcriptomic analysis showed DMBT1 dramatically downregulated in dysplastic foci compared with normal-adjacent tissue. We further integrated our datasets to generate custom colonic dysplasia scores and ligand-receptor mapping. Validation with immunofluorescence showed DMBT1 protein downregulated in dysplastic foci from three mouse models of colonic tumourigenesis. Finally, we demonstrated downregulation of DMBT1 mRNA and protein in adenomatous dysplasia from human samples. Together, our data reveal cell type-specific regulation of DMBT1, a potential mechanistic link between bacteria and colonic tumourigenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE270726 | GEO | 2025/01/13

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Leber2015 - Mucosal immunity and gut microbiome interaction during C. difficile infection This model is described in the article: Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection. Leber A, Viladomiu M, Hontecillas R, Abedi V, Philipson C, Hoops S, Howard B, Bassaganya-Riera J. PLoS ONE 2015; 10(7): e0134849 Abstract: Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17) effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg) cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions. This model is hosted on BioModels Database and identified by: BIOMD0000000583. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Multi-omic spatial atlas shows Deleted inMalignantBrain Tumours 1 (DMBT1) glycoprotein is lost in colonic dysplasia I

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets