Department of Dermatology.
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Curr Opin Rheumatol. 2024 Nov 1;36(6):379-386. doi: 10.1097/BOR.0000000000001047. Epub 2024 Sep 11.
Scleroderma and other fibrotic diseases have been investigated using single-cell RNA sequencing (scRNA-Seq), which has demonstrated enrichment in myeloid cell populations in multiple tissues. However, scRNA-Seq studies are inconsistent in their nomenclature of myeloid cell types, including dendritic cells, monocytes, and macrophages. Using cell type-defining gene signatures, I propose a unified nomenclature through analysis of myeloid cell enrichment across fibrotic tissues.
scRNA-Seq of human blood and skin identified a new subset of dendritic cells called DC3. DC3 express similar inflammatory genes to monocytes, including FCN1 , IL1B, VCAN, S100A8, S100A9 , and S100A12 . DC3 can be distinguished from monocytes by expression of EREG and Fc receptor genes such as FCER1A and FCGR2B . scRNA-Seq analyses of scleroderma skin and lung, idiopathic pulmonary fibrosis (IPF), COVID-19 lung fibrosis, myelofibrosis, and liver, kidney, and cardiac fibrosis all showed enrichment in myeloid cell types. Although they were called different names, studies of scleroderma skin and lung as well as liver cirrhosis datasets demonstrated enrichment in DC3. By contrast, lung, heart, and kidney fibrosis were enriched in SPP1 macrophages. High numbers of DC3 in the skin was associated with worse SSc skin and lung fibrosis severity.
scRNA-Seq of multiple diseases showed enrichment of DC3 in fibrotic skin, lung, and liver, whereas SPP1 macrophages occurred in fibrotic lung, heart, and kidney. Because DC3 and SPP1 macrophages showed organ-specific enrichment, understanding their signaling mechanisms across tissues will be important for future investigation.
硬皮病和其他纤维化疾病已通过单细胞 RNA 测序（scRNA-Seq）进行了研究，该技术在多种组织中的髓样细胞群中显示出了富集。然而，scRNA-Seq 研究在其髓样细胞类型的命名上并不一致，包括树突状细胞、单核细胞和巨噬细胞。通过使用细胞类型定义基因特征，我通过分析纤维化组织中的髓样细胞富集，提出了一种统一的命名法。
对人类血液和皮肤的 scRNA-Seq 鉴定出一种称为 DC3 的新型树突状细胞亚群。DC3 表达与单核细胞相似的炎症基因，包括 FCN1、IL1B、VCAN、S100A8、S100A9 和 S100A12。DC3 可以通过表达 EREG 和 Fc 受体基因（如 FCER1A 和 FCGR2B）与单核细胞区分开来。对硬皮病皮肤和肺、特发性肺纤维化（IPF）、COVID-19 肺纤维化、骨髓纤维化以及肝、肾和心脏纤维化的 scRNA-Seq 分析均显示出髓样细胞类型的富集。尽管它们被赋予了不同的名称，但硬皮病皮肤和肺以及肝硬化数据集的研究表明 DC3 富集。相比之下，肺、心脏和肾脏纤维化富含 SPP1 巨噬细胞。皮肤中 DC3 的数量较多与更严重的 SSc 皮肤和肺部纤维化严重程度相关。
多种疾病的 scRNA-Seq 显示，DC3 在纤维化皮肤、肺和肝脏中富集，而 SPP1 巨噬细胞则在纤维化的肺、心脏和肾脏中富集。由于 DC3 和 SPP1 巨噬细胞在器官中有特异性富集，因此了解它们在跨组织中的信号传导机制将对未来的研究很重要。
