Single-cell RNA sequencing reveals the heterogeneity of myofibroblasts in wound repair

Genomics. 2025 Jan;117(1):110982. doi: 10.1016/j.ygeno.2024.110982. Epub 2024 Dec 18.

Abstract

Skin wound repair involves myofibroblasts crucial for tissue integrity. This study utilized single-cell RNA sequencing to explore myofibroblast diversity in various wound healing scenarios. Analysis of 89,148 cells from skin ulcers, keloids, and normal scars identified 13 cell clusters. Myofibroblast subcluster analysis unveiled 11 subsets, with subclusters 1 and 9 predominant in ulcers. Subcluster 1 exhibited heightened matrix metalloproteinase expression and involvement in bacterial response and angiogenesis, crucial in inflammation. Tissue validation confirmed subcluster 1 significance., while animal models supported upregulated CA12, TDO2, and IL-7R in chronic ulcers. These findings illuminate myofibroblast heterogeneity and their impact on wound healing, offering insights into potential therapeutic targets.

Keywords: Heterogeneity; Keloid; Myofibroblast; Single-cell RNA sequencing; Skin ulcer.

MeSH terms

  • Animals
  • Cicatrix / genetics
  • Cicatrix / metabolism
  • Cicatrix / pathology
  • Humans
  • Keloid / genetics
  • Keloid / metabolism
  • Keloid / pathology
  • Mice
  • Myofibroblasts* / cytology
  • Myofibroblasts* / metabolism
  • RNA-Seq
  • Sequence Analysis, RNA
  • Single-Cell Analysis*
  • Skin Ulcer / genetics
  • Skin Ulcer / metabolism
  • Skin Ulcer / pathology
  • Transcriptome
  • Wound Healing* / genetics