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A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE195516 | GEO | 2024/06/17

REPOSITORIES: GEO

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A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease [array]

Project description:The intestinal epithelium is a single-cell layer comprising a constellation of specialized cell types that functionally interconnect host physiological systems with extrinsic microbial communities, metabolites, and dietary factors1. Active renewal of the intestinal epithelium relies on stem cells that reside in invaginations of the epithelium known as crypts. Inflammatory Bowel Disease (IBD) disrupts normal functions and/or proportions of cells in the intestinal epithelium, including stem cell programming during epithelial restitution. Genome-wide association studies have provided a powerful means to identify loci and genes contributing to IBD risk and functional annotation of candidate genes have unveiled cellular programs and molecular mechanisms involved in IBD etiology. Here we find that risk for a major form of IBD, Crohn’s disease (CD), is linked to a variant of the Fibroblast Growth Factor Receptor 1 Oncogene Partner (FGFR1OP) locus, which encodes a protein of the centrosome, the microtubule organizing center that generates microtubule structures involved in cell division, polarity, and motility. Deletion of Fgfr1op in mouse intestinal epithelium impaired stem cell division and intestinal crypt architecture causing crypt loss, inflammation and death. Transcriptional, biochemical and morphological analyses demonstrated that Fgfr1op coordinates the centrosome with the actin cytoskeleton and with specialized cell junctions known as desmosomes. We conclude that a genetically inherited centrosomal defect predisposes to CD by affecting renewal of the intestinal epithelium.

2024-06-17 | GSE194311 | GEO

A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease [scRNA-Seq]

2024-06-17 | GSE194312 | GEO

A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease [RNA-Seq]

2024-06-17 | GSE195515 | GEO

A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease

Project description:A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease

| PRJNA801001 | ENA

A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease [array]

Project description:A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease [array]

| PRJNA800256 | ENA

A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease [RNA-Seq]

Project description:A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease [RNA-Seq]

| PRJNA801005 | ENA

A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease [scRNA-Seq]

Project description:A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease [scRNA-Seq]

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Spatially Resolved Insights Into Fistulating Crohn’s Disease Pathogenesis

Project description:This SuperSeries is composed of the SubSeries listed below.

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A BRCA1 coiled-coil domain variant disrupting PALB2 interaction predisposes to mammary tumors with a targetable defect in homologous recombination repair.

Project description:This SuperSeries is composed of the SubSeries listed below.

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