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

Publication Year:

2025

Authors:

Lloyd Steele, Bayanne Olabi, Kenny Roberts, Pavel V Mazin, Simon Koplev, Catherine Tudor, Benjamin Rumney, Chloe Admane, Treasa Jiang, Donovan Correa-Gallegos, Keerthi Priya Chakala, Aljes Binkevich, Nusayhah Hudaa Gopee, Alexander Predeus, Martin Prete, Elena Winheim, Karl Annusver, Agnes Forsthuber, Luc Francis, Sophie Frech, Clarisse Ganier, Thomas Layton, Yingzi Liu, Hao Yuan, Johann E Gudjonsson, Beate M Lichtenberger, Satveer Mahil, Jagdeep Nanchahal, Edel A O'Toole, Maksim V Plikus, Yuval Rinkevich, Emanuel Rognoni, Catherine H Smith, Sarah A Teichmann, Maria Kasper, April R Foster, Mohammad Lotfollahi, Muzlifah Haniffa

PubMed ID:

40993240

Funding Grants:

CIRM Scholars Comprehensive Research Training Program

Public Summary:

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.

Scientific Abstract:

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.

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

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