Spatiotemporal single-cell roadmap of human skin wound healing
Zhuang Liu, Xiaowei Bian, Lihua Luo, Åsa K. Björklund, Li Li, Letian Zhang, Yongjian Chen, Lei Guo, Juan Gao, Chunyan Cao, Jiating Wang, Wenjun He, Yunting Xiao, Liping Zhu, Karl Annusver, Nusayhah Hudaa Gopee, Daniela Basurto-Lozada, Dave Horsfall, Clare L. Bennett, Maria Kasper, Muzlifah Haniffa, Pehr Sommar, Dongqing Li, Ning Xu
Abstract
Wound 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 multi-omics analyses on human skin 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.