Traeuble Korbinian, Munz Matthias, Pauli Jessica, Sachs Nadja, Vafadarnejad Eshan, Carrillo-Roa Tania, Maegdefessel Lars, Kastner Peter, Heinig Matthias
Institute of Computational Biology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
Department of Computer Science, TUM School of Computation, Information and Technology, Technical University of Munich, Garching, Germany.
Nat Commun. 2025 Sep 10;16(1):8255. doi: 10.1038/s41467-025-63202-x.
Atherosclerosis, a major cause of cardiovascular diseases, is characterized by the buildup of lipids and chronic inflammation in the arteries, leading to plaque formation and potential rupture. Despite recent advances in single-cell transcriptomics (scRNA-seq), the underlying immune mechanisms and transformations in structural cells driving plaque progression remain incompletely defined. Existing datasets often lack comprehensive coverage and consistent annotations, limiting the utility of downstream analyses. Here, we present an integrated single-cell atlas of human atherosclerotic plaques, covering roughly 250k high-quality annotated cells. We achieve robust cell type annotations validated by expert consensus and surface protein measurements. Using this atlas, we introduce distinct markers for plaque neutrophils, identify a proangiogenic endothelial cell cluster enriched in advanced lesions, and specialized macrophage subsets. We also establish that fibromyocytes are exclusive to vascular tissue. This comprehensive atlas enables accurate automatic cell type annotation of new datasets, improves experimental design by guiding sample size and detection power, and supports the deconvolution of bulk RNA-seq data. An interactive WebUI makes these resources widely accessible.
动脉粥样硬化是心血管疾病的主要病因，其特征是动脉中脂质堆积和慢性炎症，导致斑块形成并可能破裂。尽管单细胞转录组学（scRNA-seq）最近取得了进展，但驱动斑块进展的潜在免疫机制和结构细胞中的转变仍未完全明确。现有数据集往往缺乏全面覆盖和一致注释，限制了下游分析的效用。在这里，我们展示了人类动脉粥样硬化斑块的综合单细胞图谱，涵盖约25万个高质量注释细胞。我们通过专家共识和表面蛋白测量实现了可靠的细胞类型注释。使用这个图谱，我们引入了斑块中性粒细胞的独特标记，鉴定出在晚期病变中富集的促血管生成内皮细胞簇和特殊的巨噬细胞亚群。我们还确定纤维肌细胞是血管组织所特有的。这个综合图谱能够对新数据集进行准确的自动细胞类型注释，通过指导样本量和检测能力来改进实验设计，并支持对批量RNA-seq数据的反卷积分析。一个交互式的WebUI使这些资源广泛可用。
