Pan-disease fibroblast atlas in skin fibrosis, inflammation, and cancer

Fibroblasts are essential cells that sculpt the architecture and cellular microenvironments within various tissues. Understanding fibroblast heterogeneity and their spatial context in health and disease has major clinical relevance. In this study, we constructed a spatially-resolved atlas of 357 276 human skin fibroblasts from healthy skin and 23 skin disorders. We define 6 major skin fibroblast populations in health and a further three skin disease-specific fibroblast subtypes, and demonstrate the fibroblast composition in different types of skin disease. We also show that inflammatory myofibroblasts (IL11+MMP1+CXCL5+IL7R+) present in early human wounds are a conserved fibroblast subtype in inflammatory disorders and cancer, that likely recruit neutrophils and monocytes to different human tissues. We characterise a human-specific fibroblastic reticular cell (FRC)-like subtype in the skin superficial perivascular niche and postulate their origin from prenatal skin lymphoid tissue organiser (LTo)-like cells. We provide a harmonised nomenclature for skin fibroblasts that integrates previous findings from human skin and other tissues.