Spatiotemporal Single-Cell Roadmap of Human Skin Wound Healing

Abstract

SummaryWound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell and spatial transcriptomics analyses on human skin and acute wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization. It shows that pro-inflammatory macrophages and fibroblasts sequentially support keratinocyte migration like a relay race across different healing stages. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds. Additionally, comparing human and mouse acute wound transcriptomes underscores the indispensable value of this roadmap in bridging basic research with clinical innovations.HighlightsA spatiotemporal atlas to explore humanin vivogene expression across wound healingWound margin architecture unveils a model for human re-epithelializationDistinct healing challenges in venous ulcers and diabetic foot ulcersUnique human healing traits emerge in cellular heterogeneity and gene expression