Novel integrated multiomics analysis reveals a key role for integrin beta-like 1 in wound scarring

Sang-Eun Kim, Ryota Noda, Yu-Chen Liu, Yukari Nakajima, Shoichiro Kameoka, Daisuke Motooka, Seiya Mizuno, Satoru Takahashi, Kento Takaya, Takehiko Murase, Kazuya Ikematsu, Katsiaryna Tratsiakova, Takahiro Motoyama, Masahiro Nakashima, Kazuo Kishi, Paul Martin, Shigeto Seno*, Daisuke Okuzaki*, Ryoichi Mori*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)

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 languageEnglish
Pages (from-to)122-152
Number of pages31
JournalEMBO Reports
Volume26
Issue number1
Early online date18 Nov 2024
DOIs
Publication statusPublished - 10 Jan 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Keywords

  • Skin Wound Healing
  • Multiomics
  • Scarring
  • Itgbl1
  • Inflammation

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