Colon stroma mediates an inflammation-driven fibroblastic response controlling matrix remodeling and healing
Name
journal.pbio.3001532.pdf
Description
Published version
Size
3.98 MB
Format
Adobe PDF
Checksum (MD5)
27d032bd2c267b25ca0f4cb53d07bf17
Author(s)
Jasso, Guadalupe J
Jaiswal, Alok
Varma, Mukund
Laszewski, Tyler
Grauel, Angelo
Omar, Abdifatah
Silva, Nilsa
Dranoff, Glenn
Porter, Jeffrey A
Mansfield, Keith
Date Issued
2022
Journal
PLoS Biology
Publisher
Public Library of Science (PLoS)
Citation
Jasso, Guadalupe J, Jaiswal, Alok, Varma, Mukund, Laszewski, Tyler, Grauel, Angelo et al. 2022. "Colon stroma mediates an inflammation-driven fibroblastic response controlling matrix remodeling and healing." PLoS Biology, 20 (1).
Version
Final published version
Abstract
Chronic inflammation is often associated with the development of tissue fibrosis, but how mesenchymal cell responses dictate pathological fibrosis versus resolution and healing remains unclear. Defining stromal heterogeneity and identifying molecular circuits driving extracellular matrix deposition and remodeling stands to illuminate the relationship between inflammation, fibrosis, and healing. We performed single-cell RNA-sequencing of colon-derived stromal cells and identified distinct classes of fibroblasts with gene signatures that are differentially regulated by chronic inflammation, including IL-11–producing inflammatory fibroblasts. We further identify a transcriptional program associated with trans-differentiation of mucosa-associated fibroblasts and define a functional gene signature associated with matrix deposition and remodeling in the inflamed colon. Our analysis supports a critical role for the metalloprotease Adamdec1 at the interface between tissue remodeling and healing during colitis, demonstrating its requirement for colon epithelial integrity. These findings provide mechanistic insight into how inflammation perturbs stromal cell behaviors to drive fibroblastic responses controlling mucosal matrix remodeling and healing.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1371/JOURNAL.PBIO.3001532
