Department of Surgery (H.Y., T.Z., A.S., E.D., B.L.), School of Medicine and Public Health, University of Wisconsin-Madison, Madison.
Department of Cellular and Regenerative Biology (B.L.), School of Medicine and Public Health, University of Wisconsin-Madison, Madison.
Arterioscler Thromb Vasc Biol. 2021 Mar;41(3):1158-1166. doi: 10.1161/ATVBAHA.120.315607. Epub 2021 Jan 21.
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by smooth muscle cell depletion, ECM (extracellular matrix) degradation, and infiltration of immune cells. The cellular and molecular profiles that govern the heterogeneity of the AAA aorta are yet to be elucidated. Approach and Results: We performed single-cell RNA sequencing on mouse AAA tissues. AAA was induced in C57BL/6J mice by perivascular application of CaCl. Unbiased clustering identified 12 distinct populations of 8 cell types. Percentages of each population and gene expression were compared between sham and AAA tissue. Furthermore, we characterized the transcriptional profiles and potential functional features of populations in smooth muscle cells, fibroblasts, and macrophages and revealed the unique regulons in each cell type.
Together, these data provide high-resolution insight into the complexity and heterogeneity of mouse AAA and indicate that populations within major cell types such as smooth muscle cells, fibroblasts, and macrophages may contribute differently to AAA pathogenesis. Graphic Abstract: A graphic abstract is available for this article.
腹主动脉瘤（AAA）是一种危及生命的血管疾病，其特征为平滑肌细胞耗竭、细胞外基质（ECM）降解和免疫细胞浸润。指导 AAA 主动脉异质性的细胞和分子特征尚待阐明。
我们对小鼠 AAA 组织进行了单细胞 RNA 测序。通过血管周围应用 CaCl2 在 C57BL/6J 小鼠中诱导 AAA。无偏聚类鉴定出 8 种细胞类型的 12 个不同群体。比较假手术和 AAA 组织中每个群体和基因表达的百分比。此外，我们描述了平滑肌细胞、成纤维细胞和巨噬细胞中各群体的转录谱和潜在功能特征，并揭示了每种细胞类型的独特调控网络。
这些数据共同为我们提供了关于小鼠 AAA 复杂性和异质性的高分辨率见解，并表明平滑肌细胞、成纤维细胞和巨噬细胞等主要细胞类型内的群体可能对 AAA 的发病机制有不同的贡献。
