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

IF 27.6 1区医学 Q1 IMMUNOLOGY

Nature Immunology Pub Date : 2025-09-24 DOI:10.1038/s41590-025-02267-8

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

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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. Steele et al. use single-cell RNA sequencing and spatial transcriptomics to provide an atlas of adult human skin fibroblasts in healthy and diseased human skin.

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人类皮肤成纤维细胞的单细胞和空间基因组图谱揭示了组织中共享的与疾病相关的成纤维细胞亚型。

成纤维细胞塑造各种组织的结构和细胞微环境。在这里，我们构建了来自健康皮肤和23种皮肤病的人皮肤成纤维细胞的空间分辨图谱，并与14种跨组织疾病进行了比较。我们在健康中定义了六种主要的皮肤成纤维细胞亚型，三种是疾病特异性的。我们进一步描述了两种成纤维细胞亚型，因为它们在组织中是保守的，并且与免疫相关。第一种，F3：纤维母细胞网状细胞样成纤维细胞（CCL19+CD74+HLA-DRA+），是一种纤维母细胞网状细胞样亚型，预计可维持浅表血管周围免疫生态位。第二种，F6：炎性肌成纤维细胞（IL11+MMP1+CXCL8+IL7R+），是早期人类皮肤伤口、有疤痕风险的炎症性疾病和癌症的特征。F6：炎性肌成纤维细胞可在人体多个组织中募集中性粒细胞、单核细胞和B细胞。我们的研究为健康和疾病中的皮肤成纤维细胞提供了一个统一的命名法，并结合了跨组织发现和临床皮肤病概况。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Immunology 医学-免疫学

CiteScore

40.00

自引率

2.30%

发文量

248

审稿时长

4-8 weeks

期刊介绍： Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.