Liu Kaidong, Cui Yanrui, Han Huiming, Guo Erliang, Shi Xingyang, Xiong Kai, Zhang Nan, Zhai Songmei, Sang Shaocong, Liu Mingyue, Chen Bo, Gu Yunyan
Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, China.
Sci Adv. 2025 Apr 4;11(14):eado0173. doi: 10.1126/sciadv.ado0173. Epub 2025 Apr 2.
Understanding the heterogeneity of fibroblasts depends on decoding the complexity of cell subtypes, their origin, distribution, and interactions with other cells. Here, we integrated 249,156 fibroblasts from 73 studies across 10 tissues to present a single-cell atlas of fibroblasts. We provided a high-resolution classification of 18 fibroblast subtypes. In particular, we revealed a previously undescribed cell population, TSPAN8 chromatin remodeling fibroblasts, characterized by high expression of genes with functions related to histone modification and chromatin remodeling. Moreover, TSPAN8 chromatin remodeling fibroblasts were detectable in spatial transcriptome data and multiplexed immunofluorescence assays. Compared with other fibroblast subtypes, TSPAN8 chromatin remodeling fibroblasts exhibited higher scores in cell differentiation and resident fibroblast, mainly interacting with endothelial cells and T cells through ligand and receptor , and their presence was associated with poor prognosis. Our analyses comprehensively defined the shared and specific characteristics of fibroblast subtypes across tissues and provided a user-friendly data portal, Fibroblast Atlas.
了解成纤维细胞的异质性取决于解读细胞亚型的复杂性、它们的起源、分布以及与其他细胞的相互作用。在此,我们整合了来自10个组织的73项研究中的249,156个成纤维细胞,以呈现成纤维细胞的单细胞图谱。我们提供了18种成纤维细胞亚型的高分辨率分类。特别是,我们发现了一个先前未描述的细胞群体,即TSPAN8染色质重塑成纤维细胞,其特征是与组蛋白修饰和染色质重塑相关功能的基因高表达。此外,在空间转录组数据和多重免疫荧光分析中可检测到TSPAN8染色质重塑成纤维细胞。与其他成纤维细胞亚型相比,TSPAN8染色质重塑成纤维细胞在细胞分化和驻留成纤维细胞方面表现出更高的评分,主要通过配体 和受体 与内皮细胞和T细胞相互作用,并且它们的存在与预后不良相关。我们的分析全面定义了不同组织中成纤维细胞亚型的共同和特定特征,并提供了一个用户友好的数据门户,即成纤维细胞图谱。