Spatiotemporal single-cell roadmap of human skin wound healing
Journal article, 2025
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.
scRNA-seq
acute wound
chronic wounds
diabetic foot ulcer
wound healing
venous ulcer
spatial transcriptomics
Author
Zhuang Liu
Karolinska Institutet
Xiaowei Bian
Karolinska Institutet
Lihua Luo
Karolinska Institutet
Åsa Björklund
Chalmers, Life Sciences, Systems and Synthetic Biology
National Bioinformatics Infrastructure Sweden (NBIS)
Li Li
Chinese Academy of Medical Sciences
Letian Zhang
Karolinska Institutet
Yongjian Chen
Karolinska Institutet
Lei Guo
Chinese Academy of Medical Sciences
Juan Gao
Chinese Academy of Medical Sciences
Chunyan Cao
Chinese Academy of Medical Sciences
Jiating Wang
Chinese Academy of Medical Sciences
Wenjun He
Soochow University
Yunting Xiao
Chinese Academy of Medical Sciences
Liping Zhu
Chinese Academy of Medical Sciences
Karl Annusver
Karolinska Institutet
Nusayhah Hudaa Gopee
Newcastle University
Daniela Basurto-Lozada
Wellcome Trust Sanger Institute
Newcastle University
David Horsfall
Newcastle University
Wellcome Trust Sanger Institute
Clare L. Bennett
University College London (UCL)
Maria Kasper
Karolinska Institutet
Muzlifah Haniffa
NHS Foundation Trust
Wellcome Trust Sanger Institute
Newcastle University
Pehr Sommar
Karolinska University Hospital
Dongqing Li
Chinese Academy of Medical Sciences
Ning Xu Landén
Karolinska Institutet
Cell Stem Cell
1934-5909 (ISSN) 18759777 (eISSN)
Vol. 32 3 479-498.e8Subject Categories (SSIF 2025)
Cell and Molecular Biology
Dermatology and Venereal Diseases
Surgery
DOI
10.1016/j.stem.2024.11.013
PubMed
39729995