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.
venous ulcer
scRNA-seq
wound healing
acute wound
spatial transcriptomics
chronic wounds
diabetic foot ulcer
Author
Zhuang Liu
Karolinska Institutet
Xiaowei Bian
Karolinska Institutet
Lihua Luo
Karolinska Institutet
Åsa Björklund
National Bioinformatics Infrastructure Sweden (NBIS)
Chalmers, Life Sciences, Systems and Synthetic Biology
Li Li
China Academy of Chinese Medical Sciences
Letian Zhang
Karolinska Institutet
Yongjian Chen
Karolinska Institutet
Lei Guo
China Academy of Chinese Medical Sciences
Juan Gao
China Academy of Chinese Medical Sciences
Chunyan Cao
China Academy of Chinese Medical Sciences
Jiating Wang
China Academy of Chinese Medical Sciences
Wenjun He
Soochow University
Yunting Xiao
China Academy of Chinese Medical Sciences
Liping Zhu
China Academy of Chinese Medical Sciences
Karl Annusver
Karolinska Institutet
Nusayhah Hudaa Gopee
Newcastle University
Daniela Basurto-Lozada
Newcastle University
Wellcome Trust Sanger Institute
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
China Academy of Chinese 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