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

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

doi:10.1038/s41590-025-02267-8

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

Nat Immunol. 2025 Oct;26(10):1807-1820. doi: 10.1038/s41590-025-02267-8. Epub 2025 Sep 24.

Authors

Lloyd Steele^{1

2}, Bayanne Olabi^{1

3}, Kenny Roberts¹, Pavel V Mazin¹, Simon Koplev⁴, Catherine Tudor¹, Benjamin Rumney¹, Chloe Admane¹, Treasa Jiang⁵, Donovan Correa-Gallegos⁶, Keerthi Priya Chakala¹, Aljes Binkevich¹, Nusayhah Hudaa Gopee^{1

3}, Alexander Predeus¹, Martin Prete¹, Elena Winheim¹, Karl Annusver⁷, Agnes Forsthuber⁸, Luc Francis⁵, Sophie Frech⁸, Clarisse Ganier⁹, Thomas Layton¹⁰, Yingzi Liu^{11

12}, Hao Yuan⁷, Johann E Gudjonsson^{13

14}, Beate M Lichtenberger⁸, Satveer Mahil⁵, Jagdeep Nanchahal¹⁰, Edel A O'Toole¹⁵, Maksim V Plikus^{11

12}, Yuval Rinkevich^{16

17}, Emanuel Rognoni¹⁵, Catherine H Smith⁵, Sarah A Teichmann^{4

18

19}, Maria Kasper⁷, April R Foster¹, Mohammad Lotfollahi^{1

4}, Muzlifah Haniffa^{20

21

22}

Affiliations

¹ Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
² Trinity College, University of Cambridge, Cambridge, UK.
³ Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle, UK.
⁴ Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
⁵ St John's Institute of Dermatology, King's College London and Guy's & St Thomas' NHS Foundation Trust, London, UK.
⁶ Institute for Stroke and Dementia Research (ISD), University Hospital (Klinikum LMU), Munich, Germany.
⁷ Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
⁸ Department of Dermatology, Medical University of Vienna, Vienna, Austria.
⁹ Institut Pasteur, Immunology department, Meta-organism Unit, Paris, France.
¹⁰ Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
¹¹ Department of Developmental and Cell Biology, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
¹² Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
¹³ Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
¹⁴ Department of Internal Medicine, Division of Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA.
¹⁵ Centre for Cell Biology and Cutaneous Research, The Faculty of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.
¹⁶ Chinese Institutes for Medical Research, Institute of Regenerative Biology and Medicine, Beijing, China.
¹⁷ Capital Medical University, Beijing, China.
¹⁸ Department of Medicine, University of Cambridge, Cambridge, UK.
¹⁹ CIFAR Macmillan Multi-scale Human Program, CIFAR, Toronto, Ontario, Canada.
²⁰ Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK. mh32@sanger.ac.uk.
²¹ Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle, UK. mh32@sanger.ac.uk.
²² CIFAR Macmillan Multi-scale Human Program, CIFAR, Toronto, Ontario, Canada. mh32@sanger.ac.uk.

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.

MeSH terms

Fibroblasts* / immunology
Fibroblasts* / metabolism
Genomics / methods
Humans
Myofibroblasts / immunology
Single-Cell Analysis / methods
Skin Diseases* / genetics
Skin Diseases* / immunology
Skin Diseases* / pathology
Skin* / cytology
Skin* / immunology
Skin* / pathology

Abstract

MeSH terms

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