Single-Cell RNA Sequencing Redefines Macrophage Heterogeneity and Function in Wound Healing

Skin wound healing is a complex biological process that involves various cell types, molecular signals, and intricate regulatory networks. The specific cellular composition and dynamic characteristics during wound healing remain poorly understood despite their significant importance. Single-cell sequencing (SCS) emerges as a transformative tool in this context, enabling the exploration of cellular heterogeneity, underlying molecular mechanisms, and cell-to-cell interactions in wound healing. This paper reviews advancements in SCS technology and elucidates the critical role of macrophages in the healing process. Macrophages are essential for restoring tissue homeostasis by removing cellular debris, remodelling the extracellular matrix, and secreting key cytokines and growth factors. Importantly, SCS highlights that macrophages exhibit heterogeneity, functional diversity, and dynamic variation throughout the various stages of wound healing. Notably, they can differentiate into rare subtypes, including CD301b⁺ macrophages, monocyte-derived macrophages, and tissue-resident macrophages. Moreover, this review summarises key marker genes identified in SCS-based studies of skin wound healing. Overall, these insights enhance our understanding of the roles of macrophages in wound healing at the single-cell level.