单细胞测序技术解析动脉粥样硬化巨噬细胞异质性的研究进展 Progress of Single-cell Sequencing Analyzing Macrophage Heterogeneity in Atherosclerosis

Abstract

动脉粥样硬化是冠状动脉、脑血管和外周动脉疾病的重要病理基础，动脉血管壁多种类型的细胞（如皮细胞、血管平滑肌细胞、巨噬细胞、淋巴细胞等）共同参与脂质驱动的血管炎症和动脉粥样硬化斑块形成的病理过程。动脉粥样硬化斑块内巨噬细胞具有高度异质性和复杂性，不同巨噬细胞亚群执行不同的功能，调控血管炎症反应的方向。单细胞技术是全面无偏倚分析细胞异质性的理想工具。最新单细胞研究解析了动脉粥样硬化斑块复杂的细胞和分子组成，证实斑块微环境中细胞的高度适应性和可塑性。通过高通量、高分辨率单细胞测序技术分析斑块内巨噬细胞的状态、来源、动态转化轨迹、细胞间通讯及分子调控机制，有助于全面、深入理解动脉粥样硬化的发生、发展机制，最终实现临床精准靶向治疗。本文综述单细胞测序技术在揭示人和小鼠动脉粥样硬化斑块内巨噬细胞表型、分布与功能异质性方面的最新研究进展，并讨论其局限性及未来应用前景。 Abstract: Atherosclerosis is the most common underlying pathology of coronary artery disease, cerebrovascular disease and peripheral artery disease. A variety of cell types in arterial wall (including endothelial cells, vascular smooth muscle cells, macrophages and lymphocytes, etc.) are involved in lipid-driven chronic vascular inflammation and atherosclerotic plaque formation. Plaque macrophages are highly heterogeneous and complex, and different subsets of macrophages perform different function, modulating the direction of vascular inflammatory response. The single-cell sequencing technology is a kind of ideal tool for analyzing cells heterogeneity. Recent single-cell studies have revealed the complex cellular and molecular composition of human atherosclerotic plaques, suggesting a remarkable cell adaptation and plasticity in plaque microenvironment. The high-throughput and high-resolution single-cell sequencing studies may uncover the status, origin, dynamic transformation trajectory, cell communication and molecular regulatory mechanism of plaque macrophages, which will be helpful for a comprehensive and in-depth understanding of the occurrence and development of atherosclerosis, ultimately to promote clinical precise medicine. This review mainly introduced the progress of the single-cell sequencing technology in the phenotype, distribution and functional heterogeneity of macrophages in human and mice atherosclerotic plaques, and discussed the limitations and the future application prospect.

Keywords

• 动脉粥样硬化
• 巨噬细胞
• 单细胞测序
• 细胞异质性
• 斑块
• 动脉
• atherosclerosis
• macrophage
• single-cell sequencing
• cell heterogeneity
• plaque
• artery