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

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

PROVIDER: PRJNA1149687 | ENA |

REPOSITORIES: ENA

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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.

2025-08-23 | GSE275144 | GEO

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.

2025-09-17 | GSE296331 | GEO

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

2025-08-23 | GSE275148 | GEO

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

2025-08-23 | GSE275145 | GEO

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]

| PRJNA1258944 | ENA

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

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

| PRJNA1149688 | ENA

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

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

| PRJNA1149690 | ENA

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

| PRJNA623563 | ENA

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

Project description:Crohn’s disease is characterized by transmural inflammation and therefore the mesenteric immune compartment has gained interest. However, its significance in Crohn’s disease is largely unclear. Macrophages are plastic cells that adapt their phenotype to environmental stimuli resulting in inflammatory and regulatory macrophage subsets. Hence, their distribution can reflect the overall nature of an immune infiltrate. We show that mesenteric macrophages contain two populations, characterized as CD11b-high and CD11b-dim. The CD11b-dim population is characterized by expression of regulatory markers CD206, CD200R, CD163, PD-L2, CD32. CD11b-high macrophages display an IFNγ induced signature and produce high levels of calprotectin. CD11b-dim and CD11b-high populations were comparable between Crohn’s disease and other indications in expression pattern, but the CD11b-high population was strongly overrepresented in this patient group.

2021-04-07 | GSE148233 | 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.

2023-09-06 | GSE227376 | GEO

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