Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis.
Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis.
复制标题
综合单细胞荟萃分析揭示了人类动脉粥样硬化中与疾病相关的血管细胞状态和标志物。
DOI：
10.1016/j.celrep.2023.113380
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发表时间：
2023
期刊：
影响因子：
8.8
通讯作者：
Mayr
中科院分区：
文献类型：
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作者：
Mosquera,JoseVerdezoto;Auguste,Gaëlle;Wong,Doris;Turner,AdamW;Hodonsky,ChaniJ;Alvarez-Yela,AstridCatalina;Song,Yipei;Cheng,Qi;LinoCardenas,ChristianL;Theofilatos,Konstantinos;Bos,Maxime;Kavousi,Maryam;Peyser,PatriciaA;Mayr
冠状动脉疾病（CAD）的特征是动脉壁中形成动脉粥样硬化斑块。 CAD 进展涉及血管和免疫细胞谱系之间复杂的相互作用和表型可塑性。单细胞 RNA 序列 (scRNA-seq) 研究强调了谱系特异性转录组特征，但人类细胞表型仍然存在争议。在这里，我们对 22 个 scRNA-seq 文库进行了综合荟萃分析，以生成包含 118,578 个细胞的人类动脉粥样硬化综合图谱。除了表征颗粒细胞类型多样性和通讯之外，我们还利用该图谱来深入了解平滑肌细胞 (SMC) 的调节。我们整合了全基因组关联研究数据，并揭示了调节 SMC 表型在 CAD、心肌梗死和冠状动脉钙化中的关键作用。最后，我们将纤维肌细胞/纤维软骨形成 SMC 标记物（LTBP1 和 CRTAC1）确定为动脉粥样硬化进展的代表，并通过组学和空间成像分析对其进行验证。总之，我们创建了人类动脉粥样硬化的统一图谱，为心血管疾病的细胞状态特异性机制和转化研究提供信息。
Coronary artery disease (CAD) is characterized by atherosclerotic plaque formation in the arterial wall. CAD progression involves complex interactions and phenotypic plasticity among vascular and immune cell lineages. Single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures, but human cell phenotypes remain controversial. Here, we perform an integrated meta-analysis of 22 scRNA-seq libraries to generate a comprehensive map of human atherosclerosis with 118,578 cells. Besides characterizing granular cell-type diversity and communication, we leverage this atlas to provide insights into smooth muscle cell (SMC) modulation. We integrate genome-wide association study data and uncover a critical role for modulated SMC phenotypes in CAD, myocardial infarction, and coronary calcification. Finally, we identify fibromyocyte/fibrochondrogenic SMC markers (LTBP1andCRTAC1) as proxies of atherosclerosis progression and validate these through omics and spatial imaging analyses. Altogether, we create a unified atlas of human atherosclerosis informing cell state-specific mechanistic and translational studies of cardiovascular diseases.