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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. • Single-cell sequencing maps wound healing stages, highlighting myofibroblasts' critical role in tissue repair. • Subclusters 1 and 9 in skin ulcers boost MMP gene expression, hidering collagen and wound healing. • Differential genes CA12, TDO2, IL-7R in subcluster 1 are explored as biomarkers for chronic wound diagnosis and therapy.
Liu et al. (Thu,) studied this question.