威康桑格研究所Muzlifah Haniffa研究团队近日取得一项新成果。经过不懈努力，他们报道了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。这一研究成果于2025年9月24日发表在国际顶尖学术期刊《自然—免疫学》上。

在这里，研究团队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。小组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。研究人员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。他们的研究为健康和疾病中的皮肤成纤维细胞提供了统一的命名法，并结合了跨组织发现和临床皮肤病概况。

据介绍，成纤维细胞塑造了各种组织的结构和细胞微环境。

附：英文原文

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

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

Issue&Volume: 2025-09-24

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.

DOI: 10.1038/s41590-025-02267-8

Source: https://www.nature.com/articles/s41590-025-02267-8