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Coupled single-cell and bulk RNA-seq analysis reveals the engulfment role of endothelial cells in atherosclerosis
Genes & Diseases ( IF 6.8 ) Pub Date : 2024-03-02 , DOI: 10.1016/j.gendis.2024.101250
Jianxiong Xu , Jinxuan Wang , Hongping Zhang , Yidan Chen , Xiaojuan Zhang , Ying Zhang , Ming Xie , Jun Xiao , Juhui Qiu , Guixue Wang

The clearance of apoptotic cell debris, containing professional phagocytosis and non-professional phagocytosis, is essential for maintaining the homeostasis of healthy tissues. Here, we discovered that endothelial cells could engulf apoptotic cell debris in atherosclerotic plaque. Single-cell RNA sequencing (RNA-seq) has revealed a unique endothelial cell subpopulation in atherosclerosis, which was strongly associated with vascular injury-related pathways. Moreover, integrated analysis of three vascular injury-related RNA-seq datasets showed that the expression of scavenger receptor class B type 1 (SR-B1) was up-regulated and specifically enriched in the phagocytosis pathway under vascular injury circumstances. Single-cell RNA-seq and bulk RNA-seq indicate that SR-B1 was highly expressed in a unique endothelial cell subpopulation of mouse aorta and strongly associated with the reorganization of cellular adherent junctions and cytoskeleton which were necessary for phagocytosis. Furthermore, SR-B1 was strongly required for endothelial cells to engulf apoptotic cell debris in atherosclerotic plaque of both mouse and human aorta. Overall, this study demonstrated that apoptotic cell debris could be engulfed by endothelial cells through SR-B1 and associated with the reorganization of cellular adherent junctions and cytoskeleton.

中文翻译:

单细胞和批量 RNA-seq 耦合分析揭示内皮细胞在动脉粥样硬化中的吞噬作用

凋亡细胞碎片的清除,包括专业吞噬作用和非专业吞噬作用,对于维持健康组织的稳态至关重要。在这里,我们发现内皮细胞可以吞噬动脉粥样硬化斑块中的凋亡细胞碎片。单细胞 RNA 测序 (RNA-seq) 揭示了动脉粥样硬化中独特的内皮细胞亚群,该亚群与血管损伤相关途径密切相关。此外,对三个血管损伤相关RNA-seq数据集的综合分析表明,在血管损伤情况下,B型清道夫受体1型(SR-B1)的表达上调,并且在吞噬途径中特异性富集。单细胞RNA-seq和bulk RNA-seq表明SR-B1在小鼠主动脉独特的内皮细胞亚群中高表达,并且与吞噬作用必需的细胞粘附连接和细胞骨架的重组密切相关。此外,内皮细胞吞噬小鼠和人类主动脉动脉粥样硬化斑块中的凋亡细胞碎片都强烈需要SR-B1。总的来说,这项研究表明,凋亡细胞碎片可以通过 SR-B1 被内皮细胞吞噬,并与细胞粘附连接和细胞骨架的重组相关。
更新日期:2024-03-02
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