Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease
Open accessAbstract
Intestinal mesenchymal cells play essential roles in epithelial homeostasis, matrix remodeling, immunity, and inflammation. But the extent of heterogeneity within the colonic mesenchyme in these processes remains unknown. Using unbiased single-cell profiling of over 16,500 colonic mesenchymal cells, we reveal four subsets of fibroblasts expressing divergent transcriptional regulators and functional pathways, in addition to pericytes and myofibroblasts. We identified a niche population located in proximity to epithelial crypts expressing SOX6, F3 (CD142), and WNT genes essential for colonic epithelial stem cell function. In colitis, we observed dysregulation of this niche and emergence of an activated mesenchymal population. This subset expressed TNF superfamily member 14 (TNFSF14), fibroblastic reticular cell-associated genes, IL-33, and Lysyl oxidases. Further, it induced factors that impaired epithelial proliferation and maturation and contributed to oxidative stress and disease severity in vivo. Our work defines how the colonic mesenchyme remodels to fuel inflammation and barrier dysfunction in IBD.
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Significant myofibroblast functional diversity exists during skin injury and ageing.
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From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [27]
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- Authors
- Kinchen, J., Chen, H. H., Parikh, K., Antanaviciute, A., Jagielowicz, M., Fawkner-Corbett, D., Ashley, N., Cubitt, L., Mellado-Gomez, E., Attar, M., Sharma, E., Wills, Q., Bowden, R., Richter, F. C., Ahern, D., Puri, K. D., Henault, J., Gervais, F., Koohy, H., & Simmons, A.
- Affiliations
- John Radcliffe Hospital (GB)
- Centre for Human Genetics (GB)
- University of Oxford (GB)
- Achieve Life Sciences (Canada) (CA)
- Corresponding author
- Simmons, Alison
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 175
- Issue
- 2
- Pages
- 372-386.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6176871
- OpenAlex
- W2894232765
- Cited by
- 745
- References
- 44
- Citations by year
- 2026: 106 · 2025: 100 · 2024: 108 · 2023: 114 · 2022: 106 · 2021: 100 · 2020: 77 · 2019: 32 · 2018: 1
- FWCI
- 32.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes for Health Research (NIHR-RP-R3-12-026)
- Wellcome (102974/Z/13/Z)
- Crohn’s and Colitis UK
- Lee Placito Medical Fund
- Medical Research CouncilMedical Research Council (MRC)
- Abbvie
- Celgene
- Joint Royal College of Surgeons of England and British Association of Paediatric Surgeons
- Wellcome Trust
- NIHR Oxford
- Biomedical Research Centre
- Thames Valley Local Clinical Research Network
- Oxford Single Cell Consortium
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- inflammatory bowel disease, colitis, pericytes, myofibroblasts, SOX6, Wnt signaling, epithelial stem cells, TNFSF14, fibroblastic reticular cells, IL-33, lysyl oxidase, oxidative stress, epithelial barrier dysfunction, single-cell profiling
- MeSH terms
- RAW 264.7 Cells, Animals, Colitis, Colon, Epithelial Cells, Fibroblasts, Homeostasis, Humans, Inflammation, Intestinal Mucosa, Intestines, Mesoderm, Mice, Inbred C57BL, Thromboplastin, Inflammatory Bowel Diseases, Genetic Heterogeneity, Pericytes, Cell Proliferation, Mice, Tumor Necrosis Factor Ligand Superfamily Member 14, SOXD Transcription Factors, Myofibroblasts, Single-Cell Analysis, Mesenchymal Stem Cells, Wnt Signaling Pathway
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