A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues

Journal article

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+CD74+HLA-DRA+), is a fibroblastic reticular cell-like subtype that is predicted to maintain the superficial perivascular immune niche. The second, F6: inflammatory myofibroblasts (IL11+MMP1+CXCL8+IL7R+), 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: Steele, L; Olabi, B; Roberts, K; Mazin, PV; Koplev, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Immunology
• Publication date: 2025-09-24
• Acceptance date: 2025-08-05
• DOI: 10.1038/s41590-025-02267-8
• EISSN: 1529-2916
• ISSN: 1529-2908
• Language: English
• Keywords: Myofibroblast; Reticular connective tissue; Human skin; Dermal fibroblast