Single-cell and bulk RNA sequencing of mouse atherosclerosis disease stage course [scRNA-Seq]

Atherosclerotic coronary artery disease (CAD) development encompasses endothelial dysfunction, vascular infiltration of immune cells and smooth muscle cell dedifferentiation. However, the specific disease-associated transcriptional changes occurring within each of the major lesional cell types remain incompletely characterized. Here, we identify disease-associated cell states within the major aortic cell types and investigate the similarities and differences in their gene signatures compared to each other and to healthy (non-diseased) cells. By integrating human genetic association data and generating polygenic risk scores, we further use the atherosclerosis-associated cell state gene signatures to interrogate how the perturbed states of different lesional cell types contribute to the genetic risk for CAD.动脉粥样硬化性冠状动脉疾病（Atherosclerotic coronary artery disease, CAD）的发生发展涵盖内皮功能障碍、免疫细胞血管浸润及平滑肌细胞去分化过程。然而，目前仍未完全阐明每种主要病变细胞类型内所发生的疾病特异性转录组变化。本研究鉴定了主要主动脉细胞类型中的疾病相关细胞状态，并对比各细胞类型之间以及与健康（非病变）细胞的基因表达特征，探究其异同。在此基础上，本研究整合人类遗传关联数据并构建多基因风险评分，利用动脉粥样硬化相关细胞状态的基因特征，解析不同病变细胞类型的紊乱状态如何影响冠心病的遗传易感性。