A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues
Fibroblasts sculpt the architecture and cellular microenvironments of various tissues. Here we constructed a spatially resolved atlas of human skin fibroblasts from healthy skin and 23 skin diseases, with comparison to 14 cross-tissue diseases. We define six major skin fibroblast subtypes in health and three that are disease-specific. We characterize two fibroblast subtypes further as they are conserved across tissues and are immune-related. The first, F3: fibroblastic reticular cell-like fibroblast (CCL19<sup>+</sup>CD74<sup>+</sup>HLA-DRA<sup>+</sup>), is a fibroblastic reticular cell-like subtype that is predicted to maintain the superficial perivascular immune niche. The second, F6: inflammatory myofibroblasts (IL11<sup>+</sup>MMP1<sup>+</sup>CXCL8<sup>+</sup>IL7R<sup>+</sup>), characterizes early human skin wounds, inflammatory diseases with scarring risk and cancer. F6: inflammatory myofibroblasts were predicted to recruit neutrophils, monocytes and B cells across multiple human tissues. Our study provides a harmonized nomenclature for skin fibroblasts in health and disease, contextualized with cross-tissue findings and clinical skin disease profiles.
Authors
- Pavel Mazin (ORCID: https://orcid.org/0000-0001-9268-3352)
- Treasa Jiang (ORCID: https://orcid.org/0009-0002-5786-9340)
- Agnes Forsthuber (ORCID: https://orcid.org/0000-0001-6396-0090)
- Catherine Tudor (ORCID: https://orcid.org/0000-0003-2093-9683)
- Sarah Amalia Teichmann (ORCID: https://orcid.org/0000-0002-6294-6366)
- Yuval Rinkevich (ORCID: https://orcid.org/0000-0003-3658-0257)
- Sophie Frech (ORCID: https://orcid.org/0000-0002-6190-8595)
- Donovan Correa‐Gallegos (ORCID: https://orcid.org/0000-0001-7028-2478)
- Nusayhah Hudaa Gopee (ORCID: https://orcid.org/0000-0001-8507-5682)
- Maria Kasper (ORCID: https://orcid.org/0000-0002-6117-2717)
- Emanuel Rognoni (ORCID: https://orcid.org/0000-0001-6050-2860)
- Simon Koplev (ORCID: https://orcid.org/0000-0002-8586-5614)
- Beate M. Lichtenberger (ORCID: https://orcid.org/0000-0001-6882-0257)
- Kenny S. Roberts (ORCID: https://orcid.org/0000-0001-6155-0821)
- Alexander V. Predeus (ORCID: https://orcid.org/0000-0002-2750-1599)
- Chloe Admane (ORCID: https://orcid.org/0009-0005-9327-9008)
- Maksim V. Plikus (ORCID: https://orcid.org/0000-0002-8845-2559)
- Elena Winheim (ORCID: https://orcid.org/0000-0002-0364-662X)
- Yingzi Liu (ORCID: https://orcid.org/0000-0002-8704-4756)
- Satveer K. Mahil (ORCID: https://orcid.org/0000-0003-4692-3794)
- Johann Eli Gudjonsson (ORCID: https://orcid.org/0000-0002-0080-0812)
- Luc Francis (ORCID: https://orcid.org/0009-0006-2476-025X)
- Muzlifah A. Haniffa (ORCID: https://orcid.org/0000-0002-3927-2084)
- Benjamin Rumney (ORCID: https://orcid.org/0000-0001-7854-9739)
- Martin Prete (ORCID: https://orcid.org/0000-0002-5946-821X)
- Lloyd Steele (ORCID: https://orcid.org/0000-0003-4745-1338)
- T. B. Layton (ORCID: https://orcid.org/0000-0003-1934-7234)
- Mohammad Lotfollahi (ORCID: https://orcid.org/0000-0001-6858-7985)
- Jagdeep Nanchahal (ORCID: https://orcid.org/0000-0002-9579-9411)
- Bayanne Olabi (ORCID: https://orcid.org/0000-0002-4786-7838)
- Clarisse Gânier
- Catherine Smith (ORCID: https://orcid.org/0000-0001-9918-1144)
- Karl Annusver (ORCID: https://orcid.org/0000-0002-9515-7216)
- Edel A. O’Toole (ORCID: https://orcid.org/0000-0002-4084-4836)
- April Foster (ORCID: https://orcid.org/0000-0002-5397-4365)
- Hao Yuan (ORCID: https://orcid.org/0000-0002-4200-3600)
- Keerthi Priya Chakala
- Aljes Binkevich
Institutions
- Canadian Institute for Advanced Research (CA)
- Institut Pasteur (FR)
- Queen Mary University of London (GB)
- Capital Medical University (CN)
- King's College London (GB)
- Guy's and St Thomas' NHS Foundation Trust (GB)
- University of California, Irvine (US)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- University of Michigan (US)
- Nuffield Orthopaedic Centre (GB)
- Wellcome Sanger Institute (GB)
- Karolinska Institutet (SE)
- LMU Klinikum (DE)
- University of Oxford (GB)
- NIHR Newcastle Biomedical Research Centre (GB)
- Regenerative Medicine Institute (MX)
- Medical University of Vienna (AT)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Immunology
- Published
- 2025-09-24
- DOI
- https://doi.org/10.1038/s41590-025-02267-8
- Citations
- 21
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 16.93