Abstract
Exacerbation of scarring can originate from a minority fibroblast population that has undergone inflammatory-mediated genetic changes within the wound microenvironment. The fundamental relationship between molecular and spatial organization of the repair process at the single-cell level remains unclear. We have developed a novel, high-resolution spatial multiomics method that integrates spatial transcriptomics with scRNA-Seq; we identified new characteristic features of cell–cell communication and signaling during the repair process. Data from PU.1-/- mice, which lack an inflammatory response, combined with scRNA-Seq and Visium transcriptomics, led to the identification of nine genes potentially involved in inflammation-related scarring, including integrin beta-like 1 (Itgbl1). Transgenic mouse experiments confirmed that Itgbl1-expressing fibroblasts are required for granulation tissue formation and drive fibrogenesis during skin repair. Additionally, we detected a minority population of Acta2high-expressing myofibroblasts with apparent involvement in scarring, in conjunction with Itgbl1 expression. IL1β signaling inhibited Itgbl1 expression in TGFβ1-treated primary fibroblasts from humans and mice. Our novel methodology reveal molecular mechanisms underlying fibroblast–inflammatory cell interactions that initiate wound scarring.
Original language | English |
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Pages (from-to) | 122-152 |
Number of pages | 31 |
Journal | EMBO Reports |
Volume | 26 |
Issue number | 1 |
Early online date | 18 Nov 2024 |
DOIs | |
Publication status | Published - 10 Jan 2025 |
Bibliographical note
Publisher Copyright:© The Author(s) 2024.
Keywords
- Skin Wound Healing
- Multiomics
- Scarring
- Itgbl1
- Inflammation