Liu Zhuang, Bian Xiaowei, Luo Lihua, Björklund Åsa K, Li Li, Zhang Letian, Chen Yongjian, Guo Lei, Gao Juan, Cao Chunyan, Wang Jiating, He Wenjun, Xiao Yunting, Zhu Liping, Annusver Karl, Gopee Nusayhah Hudaa, Basurto-Lozada Daniela, Horsfall David, Bennett Clare L, Kasper Maria, Haniffa Muzlifah, Sommar Pehr, Li Dongqing, Landén Ning Xu
Dermatology and Venereology Division, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden.
Department of Life Science, National Bioinformatics Infrastructure Sweden, Göteborg, Sweden; Science for Life Laboratory, Chalmers University of Technology, 41296 Göteborg, Sweden.
Cell Stem Cell. 2025 Mar 6;32(3):479-498.e8. doi: 10.1016/j.stem.2024.11.013. Epub 2024 Dec 26.
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.
伤口愈合对人类健康至关重要，然而人类伤口修复中细胞动力学和协调的细节在很大程度上仍未得到探索。为了解决这个问题，我们对来自同一受试者的人类皮肤伤口组织在伤口修复的炎症、增殖和重塑阶段进行了单细胞多组学分析，以前所未有的时空分辨率监测人类皮肤伤口愈合的细胞和分子动力学。这一独特的路线图揭示了伤口边缘的细胞结构，并确定FOSL1是再上皮化的关键驱动因素。它表明促炎性巨噬细胞和成纤维细胞像接力赛一样在不同愈合阶段依次支持角质形成细胞迁移。与静脉性和糖尿病足溃疡的单细胞数据比较发现，慢性伤口中角质形成细胞迁移失败与炎症反应受损之间存在联系。此外，比较人类和小鼠急性伤口转录组强调了这一路线图在将基础研究与临床创新联系起来方面的不可或缺的价值。
