Single-Cell Transcriptomic Atlas of Different Human Cardiac Arteries Identifies Cell Types Associated With Vascular Physiology
Single-Cell Transcriptomic Atlas of Different Human Cardiac Arteries Identifies Cell Types Associated With Vascular Physiology
复制标题
不同人类心脏动脉的单细胞转录组图谱鉴定了与血管生理学相关的细胞类型
DOI：
10.1161/atvbaha.120.315373
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发表时间：
2021-04-01
影响因子：
8.7
通讯作者：
Song, Jiangping
中科院分区：
文献类型：
--
作者：
Hu, Zhan;Liu, Wendao;Song, Jiangping
补充数字内容可在文本中找到。目的：虽然已经在小鼠和非人灵长类动物中探索了动脉壁内的细胞异质性，但人类动脉壁的细胞组成尚不清楚。方法与结果：采用单细胞测序法对3例心脏移植患者无病变心脏动脉（3条主动脉、2条肺动脉和9条冠状动脉）的细胞组成进行了研究。聚类分析确定了25个亚群，代表了10种主要的动脉细胞类型：血管平滑肌细胞（4簇）、成纤维细胞（4簇）、巨噬细胞（Mφ， 4簇）、T细胞（4簇）、内皮细胞（4簇）、NK细胞（2簇）、肥大细胞（1簇）、肌成纤维细胞（1簇）、少突胶质细胞（1簇）和B/浆细胞（1簇）。心脏动脉细胞群以血管平滑肌细胞最多，其次为成纤维细胞、Mφ细胞、T细胞、内皮细胞、NK细胞等。我们比较了不同动脉的细胞组成，发现了一些动脉特异性的血管平滑肌细胞和成纤维细胞亚群。在非病变状态下，血管平滑肌细胞与成纤维细胞之间的通讯占优势。动脉粥样硬化相关基因在内皮细胞和Mφ中特别丰富，内皮细胞和免疫细胞之间的细胞间通讯预计会在动脉粥样硬化中增加。ICAM1/VCAM1 （EC1）与ITGB2（免疫细胞，特别是炎性Mφ）之间的相互作用被推测为动脉粥样硬化发病的必要条件。结论：我们建立了人类非病变心脏动脉的细胞图谱，并表征了不同心脏动脉的细胞组成。我们的研究结果可以作为识别血管疾病相关细胞群的参考，并有助于研究血管疾病的新治疗策略。
Supplemental Digital Content is available in the text. Objective: Although cellular heterogeneity within arterial walls has been explored in mice and nonhuman primates, the cellular composition of human arterial walls remains unclear. Approach and Results: The cellular composition of nondiseased cardiac arteries (3 aortas, 2 pulmonary arteries and 9 coronary arteries) from 3 heart transplantation patients were investigated by single-cell sequencing of >105 cells. Clustering analysis identified 25 subpopulations representing the 10 main arterial cell types: vascular smooth muscle cell (4 clusters), fibroblast (4 clusters), macrophage (Mφ, 4 clusters), T cell (4 clusters), endothelial cell (4 clusters), NK cell (2 clusters), mast cell (1 cluster), myofibroblast (1 cluster), oligodendrocyte (1 cluster), and B/plasma cells (1 cluster). Vascular smooth muscle cell was the largest cell population in cardiac arteries, followed by fibroblast, Mφ, T cell, endothelial cell, NK cell, and so on. We compared cellular composition among different arteries and found some artery-specific vascular smooth muscle cell and fibroblast subpopulations. The communication between vascular smooth muscle cell and fibroblast was predominant in nondiseased condition. Atherosclerosis-associated genes were particularly enriched in endothelial cell and Mφ, and intercellular communication between endothelial cell and immune cells was predicted to increase in atherosclerosis. The interaction between ICAM1/VCAM1 (EC1) and ITGB2 (immune cells, especially inflammatory Mφ) was speculated to be essential for the pathogenesis of atherosclerosis. Conclusions: We created a cell atlas of human nondiseased cardiac arteries, and characterized the cellular compositions in different cardiac arteries. Our results could be used as a reference to identify vascular disease-associated cell populations and help investigate new therapeutic strategies for vascular diseases.