MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Colon stroma mediates an inflammation-driven fibroblastic response controlling matrix remodeling and healing

Author(s)
Jasso, Guadalupe J; Jaiswal, Alok; Varma, Mukund; Laszewski, Tyler; Grauel, Angelo; Omar, Abdifatah; Silva, Nilsa; Dranoff, Glenn; Porter, Jeffrey A; Mansfield, Keith; Cremasco, Viviana; Regev, Aviv; Xavier, Ramnik J; Graham, Daniel B; ... Show more Show less
Thumbnail
DownloadPublished version (3.977Mb)
Publisher with Creative Commons License

Publisher with Creative Commons License

Creative Commons Attribution

Terms of use
Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/
Metadata
Show full item record
Abstract
<jats:p>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 <jats:italic>trans</jats:italic>-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.</jats:p>
Date issued
2022
URI
https://hdl.handle.net/1721.1/147093
Department
Massachusetts Institute of Technology. Department of Biology
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

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.