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. 2021 Mar;41(3):1158-1166.
doi: 10.1161/ATVBAHA.120.315607. Epub 2021 Jan 21.

Single-Cell RNA Sequencing Reveals Heterogeneity of Vascular Cells in Early Stage Murine Abdominal Aortic Aneurysm-Brief Report

Huan Yang #  1 , Ting Zhou #  1 , Amelia Stranz  1 , Elise DeRoo  1 , Bo Liu  1   2
Affiliations

Single-Cell RNA Sequencing Reveals Heterogeneity of Vascular Cells in Early Stage Murine Abdominal Aortic Aneurysm-Brief Report

Huan Yang et al. Arterioscler Thromb Vasc Biol. 2021 Mar.

Abstract

Objective: 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 CaCl2. 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.

Conclusions: 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.

Keywords: aortic aneurysm; extracellular matrix; inflammation; macrophages; smooth muscle cells.

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Conflict of interest statement

Disclosures

The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Identification of cell populations in mouse AAA (abdominal aortic aneurysm) tissues. Mouse aortas were perivascularly treated with NaCl (sham) or CaCl2 (AAA). The treated aortic segments were harvested 4 days after surgery. Four aortas from each condition were pooled to generate single-cell suspensions. (A) UMAP (Uniform Manifold Approximation and Projection) plot of cell clusters presented in mouse aortas (sham and AAA combined). (B) Heatmap of the top 10 enriched genes in each population. (C) Cell distributions in sham and aneurysm-prone aortas. (D) Percentages of cell populations in sham and AAA group.
Figure 2.
Figure 2.
Gene expression heterogeneity of macrophage populations. (A) Heatmap of the top 10 enriched genes in each macrophage population in comparison to the other two macrophage populations. (B) KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis of genes significantly upregulated in each macrophage population in comparison to the other two macrophage populations. (C) Volcano plot of DEGs (differentially expressed genes) in AAA (abdominal aortic aneurysm) versus sham group.
See this image and copyright information in PMC

References

    1. Lindeman JH, Matsumura JS. Pharmacologic management of aneurysms. Circ Res. 2019;124:631–646 - PMC - PubMed
    1. Daugherty A, Cassis LA. Mouse models of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2004;24:429–434 - PubMed
    1. Dale MA, Ruhlman MK, Baxter BT. Inflammatory cell phenotypes in aaas: Their role and potential as targets for therapy. Arterioscler Thromb Vasc Biol. 2015;35:1746–1755 - PMC - PubMed
    1. Wirka RC, Wagh D, Paik DT, Pjanic M, Nguyen T, Miller CL, Kundu R, Nagao M, Coller J, Koyano TK, Fong R, Woo YJ, Liu B, Montgomery SB, Wu JC, Zhu K, Chang R, Alamprese M, Tallquist MD, Kim JB, Quertermous T. Atheroprotective roles of smooth muscle cell phenotypic modulation and the tcf21 disease gene as revealed by single-cell analysis. Nat Med. 2019;25:1280–1289 - PMC - PubMed
    1. Cochain C, Vafadarnejad E, Arampatzi P, Pelisek J, Winkels H, Ley K, Wolf D, Saliba AE, Zernecke A. Single-cell rna-seq reveals the transcriptional landscape and heterogeneity of aortic macrophages in murine atherosclerosis. Circ Res. 2018;122:1661–1674 - PubMed

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