Identification of Macrophage-Dependent Fcer1g+ Mesenchymal Cells as Key Regulators of Scar Formation in Wound Healing

Scarring is a common outcome of wound healing in adult skin, often leading to fibrotic tissue that lacks the functional and aesthetic properties of normal, uninjured skin. To effectively reduce and prevent scar formation, understanding the cellular players involved in fibrosis is crucial. Among these, macrophages and mesenchymal cells have received significant attention due to their vital roles in both tissue regeneration and fibrosis. Research has shown that depleting macrophages during the early stages of wound healing reduces the number of myofibroblasts in the wound bed and delays wound closure, but results in reduced scar formation, suggesting that macrophages contribute to fibrosis by regulating mesenchymal cells. However, there remains a need for unbiased, high-throughput approaches to precisely investigate the mechanisms through which macrophages regulate and induce mesenchymal subtypes in scar formation. In this study, we performed single-cell RNA sequencing to investigate changes in mesenchymal cell subpopulations during adult skin wound healing in a conditional macrophage depletion mouse model, macrophage Fas-induced apoptosis (MaFIA). Overall design: To identify mesenchymal cell subtypes regulated by acute-phase macrophages during wound healing, we performed single-cell RNA sequencing (scRNA-seq) on 3 day-post-injury skin cells isolated from the wounds of MaFIA mice, with or without macrophage depletion.