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| Status |
Public on Jun 17, 2024 |
| Title |
A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Small intestinal spheroids from WT and Fgfr1op KO mice at day 3 post-hydroxytamoxifen in vitro (4 mice each group). Small intestinal crypt-enriched cells from WT and Fgfr1op KO mice at days 6 and 9 post-tamoxifen (3 mice each group). Scramble or shFgfr1op Caco-2 cells at day 3 post-doxycycline.
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| Contributor(s) |
Peng V, Trsan T, Xavier RJ, Colonna M |
| Citation(s) |
38942017 |
| |
| Submission date |
Jan 26, 2022 |
| Last update date |
Sep 16, 2024 |
| Contact name |
Vincent Peng |
| E-mail(s) |
vpeng@wustl.edu
|
| Organization name |
Washington University School of Medicine in St. Louis
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| Street address |
660 S. Euclid Ave.
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| City |
St. Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (26)
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| This SubSeries is part of SuperSeries: |
| GSE195516 |
A centrosomal defect of intestinal stem cells predisposes to Crohn’s Disease |
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| Relations |
| BioProject |
PRJNA801005 |
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