Single-cell RNA sequencing reveals the cellular heterogeneity of aneurysmal infrarenal abdominal aorta
Single-cell RNA sequencing reveals the cellular heterogeneity of aneurysmal infrarenal abdominal aorta
复制标题
单细胞RNA测序揭示动脉瘤性腹主动脉的细胞异质性
DOI：
10.1093/cvr/cvaa214
复制
发表时间：
2021-05-01
影响因子：
10.8
通讯作者：
Zhang, Jifeng
中科院分区：
文献类型：
--
作者：
Zhao, Guizhen;Lu, Haocheng;Zhang, Jifeng
目的动脉中含有多种类型的细胞，可导致多种血管疾病。然而，这些血管细胞在腹主动脉瘤（AAA）进展过程中的异质性和细胞反应尚未得到很好的表征。方法和结果对C57BL/6J小鼠肾下腹主动脉（IAAs）进行单细胞RNA测序。对bbb4500主动脉细胞的转录谱进行无偏聚类分析，鉴定出17个簇，代表9个细胞系，包括血管平滑肌细胞（VSMCs）、成纤维细胞、内皮细胞、免疫细胞（巨噬细胞、T细胞、B细胞和树突状细胞）。还有两种稀有细胞，包括神经细胞和红细胞。Seurat聚类分析鉴定出4个平滑肌细胞（SMC）亚群和5个单核/巨噬细胞亚群，它们具有不同的转录谱。在AAA进展过程中，三个主要的SMC亚群按比例减少，而小亚群则增加，并伴有SMC收缩标记物下调和促炎基因上调。另一种与ma相关的细胞反应是免疫细胞扩增，特别是单核/巨噬细胞。弹力蛋白酶暴露诱导主动脉巨噬细胞、血源性单核细胞和炎性巨噬细胞显著扩张和活化。我们还发现表达抗炎细胞因子的血源性修复巨噬细胞增加，这表明炎症的消退和血管修复在AAA进展过程中也持续存在。结论我们的数据确定了IAA中血管细胞与AAA疾病相关的转录特征。此外，我们表征了AAA进展过程中VSMCs和单核/巨噬细胞的异质性和细胞反应，这为他们的功能和AAA发生和进展的调节提供了见解。
Aims The artery contains numerous cell types which contribute to multiple vascular diseases. However, the heterogeneity and cellular responses of these vascular cells during abdominal aortic aneurysm (AAA) progression have not been well characterized.Methods and result Single-cell RNA sequencing was performed on the infrarenal abdominal aortas (IAAs) from C57BL/6J mice at Days 7 and 14 post-sham or peri-adventitial elastase-induced AAA. Unbiased clustering analysis of the transcriptional profiles from >4500 aortic cells identified 17 clusters representing nine-cell lineages, encompassing vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells, immune cells (macrophages, T cells, B cells, and dendritic cells), and two types of rare cells, including neural cells and erythrocyte cells. Seurat clustering analysis identified four smooth muscle cell (SMC) subpopulations and five monocyte/macrophage subpopulations, with distinct transcriptional profiles. During AAA progression, three major SMC subpopulations were proportionally decreased, whereas the small subpopulation was increased, accompanied with down-regulation of SMC contractile markers and upregulation of pro-inflammatory genes. Another MA-associated cellular response is immune cell expansion, particularly monocytes/macrophages. Elastase exposure induced significant expansion and activation of aortic resident macrophages, blood-derived monocytes and inflammatory macrophages. We also identified increased bloodderived reparative macrophages expressing anti-inflammatory cytokines suggesting that resolution of inflammation and vascular repair also persist during AAA progression.Conclusion Our data identify AAA disease-relevant transcriptional signatures of vascular cells in the IAA. Furthermore, we characterize the heterogeneity and cellular responses of VSMCs and monocytes/macrophages during AAA progression, which provide insights into their function and the regulation of AAA onset and progression.[GRAPHICS].