Objective: 

To determine cell-specific gene expression profiles that contribute to development of abdominal aortic aneurysms (AAAs).

Background: 

AAAs represent the most common pathological aortic dilation leading to the fatal consequence of aortic rupture. Both immune and structural cells contribute to aortic degeneration, however, gene specific alterations in these cellular subsets are poorly understood.

Methods: 

We performed single-cell RNA sequencing (scRNA-seq) analysis of AAAs and control tissues. AAA-related changes were examined by comparing gene expression profiles as well as detailed receptor-ligand interactions. An integrative analysis of scRNA-seq data with large genome-wide association study data was conducted to identify genes critical for AAA development.

Results: 

Using scRNA-seq we provide the first comprehensive characterization of the cellular landscape in human AAA tissues. Unbiased clustering analysis of transcriptional profiles identified seventeen clusters representing 8 cell lineages. For immune cells, clustering analysis identified 4 T-cell and 5 monocyte/macrophage subpopulations, with distinct transcriptional profiles in AAAs compared to controls. Gene enrichment analysis on immune subsets identified multiple pathways only expressed in AAA tissue, including those involved in mitochondrial dysfunction, proliferation, and cytokine secretion. Moreover, receptor-ligand analysis defined robust interactions between vascular smooth muscle cells and myeloid populations in AAA tissues. Lastly, integrated analysis of scRNA-seq data with genome-wide association study studies determined that vascular smooth muscle cell expression of SORT1 is critical for maintaining normal aortic wall function.

Conclusions: 

Here we provide the first comprehensive evaluation of single-cell composition of the abdominal aortic wall and reveal how the gene expression landscape is altered in human AAAs.

中文翻译：

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单细胞转录组学揭示平滑肌细胞的动态作用和免疫细胞亚群在人腹主动脉瘤中的富集

客观的： 

确定有助于腹主动脉瘤 (AAA) 发展的细胞特异性基因表达谱。

背景： 

AAA 代表最常见的病理性主动脉扩张，导致主动脉破裂的致命后果。免疫细胞和结构细胞都会导致主动脉变性，然而，人们对这些细胞亚群的基因特异性改变知之甚少。

方法： 

我们对 AAA 和对照组织进行了单细胞 RNA 测序 (scRNA-seq) 分析。通过比较基因表达谱以及详细的受体-配体相互作用来检查 AAA 相关的变化。对 scRNA-seq 数据与大型全基因组关联研究数据进行综合分析，以确定对 AAA 发展至关重要的基因。

结果： 

使用 scRNA-seq，我们首次提供了人类 AAA 组织中细胞景观的全面表征。转录谱的无偏聚类分析确定了代表 8 个细胞谱系的 17 个簇。对于免疫细胞，聚类分析识别出 4 个 T 细胞和 5 个单核细胞/巨噬细胞亚群，与对照相比，AAA 中具有不同的转录特征。对免疫子集的基因富集分析发现了仅在 AAA 组织中表达的多种途径，包括涉及线粒体功能障碍、增殖和细胞因子分泌的途径。此外，受体-配体分析确定了AAA 组织中血管平滑肌细胞和骨髓细胞群之间的强大相互作用。最后，对 scRNA-seq 数据与全基因组关联研究的综合分析确定，血管平滑肌细胞SORT1的表达对于维持正常的主动脉壁功能至关重要。

结论： 

在这里，我们首次对腹主动脉壁的单细胞组成进行了全面评估，并揭示了人类 AAA 中基因表达景观是如何改变的。