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Transcriptomics analysis of creeping fat from repeated colonic cautery injury mouse model and healthy controls

ABSTRACT: Transcriptomics analysis of creeping fat from repeated colonic cautery injury mouse model and healthy controls

PROVIDER: PRJNA1144832 | ENA |

REPOSITORIES: ENA

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Transcriptomics analysis of creeping fat from repeated colonic cautery injury mouse model and healthy controls

Project description:A feature of Crohn's disease is the extra-intestinal manifestation of creeping fat, defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic ileum. We modelled the phenotype by performing repeated colonic cautery in mice. In comparison to healthy controls, we found that the greatest transcriptional changes in creeping fat in mouse model are functions related to collagen production and extracellular matrix organization.

2025-08-31 | GSE274055 | GEO

Transcriptomic analysis reveals the dynamic changes of immune responses during the development of creeping fat in Crohn's disease

Project description:In Crohn's disease, creeping fat is the characteristic expansion of mesenteric adipose tissue wrapping around the inflamed intestine. Through a comparative transcriptomic analysis of creeping fat and normal-looking mesenteric adipose tissues from patients with Crohn's disease and non-Crohn's disease, we found that a dynamic transcriptional and cell compositional change occurs during the progression from non-Crohn's disease to Crohn's disease, and finally to creeping fat.

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Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures [Visium]

Project description:A significant complication of Crohn’s disease (CD) is intestinal fibrosis, which narrows the bowel lumen to cause a stricture. Creeping fat (CF) is the wrapping of mesenteric adipose tissue (MAT) around inflamed and fibrotic bowel, but its role in stricture progression in CD is unclear. In this study, we explore whether CF-derived fibroblasts, the cells primarily responsible for extracellular matrix (ECM) deposition, directly contribute to stricture progression. By performing scRNA-seq and Visium on pediatric CD strictures, we identified a CF-associated, mechanosensitive, CTHRC1+ fibroblast enriched for YAP/TAZ signaling that localized to the fibrotic CF-bowel wall interface within the stricture. We developed a novel mouse model of intestinal fibrosis that exhibited CF and used lineage tracing to show that Postn+ mouse fibroblasts, analogous to human CTHRC1+ fibroblasts, infiltrate fibrotic bowel and deposit ECM in a YAP/TAZ-dependent manner through scRNA-seq. Our findings identify mesenteric fat as a key source of pro-fibrotic fibroblasts that can be therapeutically targeted to limit intestinal fibrosis.

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Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures [Xenium]

Project description:A significant complication of Crohn’s disease (CD) is intestinal fibrosis, which narrows the bowel lumen to cause a stricture. Creeping fat (CF) is the wrapping of mesenteric adipose tissue (MAT) around inflamed and fibrotic bowel, but its role in stricture progression in CD is unclear. In this study, we explore whether CF-derived fibroblasts, the cells primarily responsible for extracellular matrix (ECM) deposition, directly contribute to stricture progression. By performing scRNA-seq, Visium and Xenium on pediatric CD strictures, we identified a CF-associated, mechanosensitive, CTHRC1+ fibroblast enriched for YAP/TAZ signaling that localized to the fibrotic CF-bowel wall interface within the stricture. We developed a novel mouse model of intestinal fibrosis that exhibited CF and used lineage tracing to show that Postn+ mouse fibroblasts, analogous to human CTHRC1+ fibroblasts, infiltrate fibrotic bowel and deposit ECM in a YAP/TAZ-dependent manner through scRNA-seq. Our findings identify mesenteric fat as a key source of pro-fibrotic fibroblasts that can be therapeutically targeted to limit intestinal fibrosis.

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Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures [Human scRNA-seq]

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Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures [Mouse scRNA-seq]

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Transcriptomics analysis of mesenteric adipose tissue from Crohn's disease patients and healthy controls [RNA-seq]

Project description:A feature of Crohn's disease is the extra-intestinal manifestation of creeping fat, defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic ileum. In comparison to healthy controls, we found that the greatest transcriptional changes in creeping fat are functions related to immune response to bacterial products.

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Macrophages in Crohn’s disease creeping fat are predominantly inflammatory and produce calprotectin

Project description:Macrophages in Crohn’s disease creeping fat are predominantly inflammatory and produce calprotectin

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Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans

Project description:A mysterious feature of Crohn’s disease (CD) is the extra-intestinal manifestation of "creeping fat" (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explored whether microbial translocation in human intestinal inflammation serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections. We identified Clostridium innocuum as a signature of this consortium with strain variation between the mucosa and adipose. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages leading to an adipose tissue barrier that prevents further dissemination of bacteria.

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Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures [Xenium]

Project description:Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures [Xenium]

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