Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis

Mosquera, Jose Verdezoto and Auguste, Gaëlle and Wong, Doris and Turner, Adam W. and Hodonsky, Chani J. and Alvarez-Yela, Astrid Catalina and Song, Yipei and Cheng, Qi and Lino Cardenas, Christian L. and Theofilatos, Konstantinos and Bos, Maxime and Kavousi, Maryam and Peyser, Patricia A. and Mayr, Manuel and Kovacic, Jason C. and Björkegren, Johan L.M. and Malhotra, Rajeev and Stukenberg, P. Todd and Finn, Aloke V. and van der Laan, Sander W. and Zang, Chongzhi and Sheffield, Nathan C. and Miller, Clint L. (2023) Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis. Cell Reports, 42 (11). p. 113380. ISSN 22111247

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Coronary artery disease (CAD) is characterized by atherosclerotic plaque formation in the arterial wall. CAD progression involves complex interactions and phenotypic plasticity among vascular and immune cell lineages. Single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures, but human cell phenotypes remain controversial. Here, we perform an integrated meta-analysis of 22 scRNA-seq libraries to generate a comprehensive map of human atherosclerosis with 118,578 cells. Besides characterizing granular cell-type diversity and communication, we leverage this atlas to provide insights into smooth muscle cell (SMC) modulation. We integrate genome-wide association study data and uncover a critical role for modulated SMC phenotypes in CAD, myocardial infarction, and coronary calcification. Finally, we identify fibromyocyte/fibrochondrogenic SMC markers (LTBP1 and CRTAC1) as proxies of atherosclerosis progression and validate these through omics and spatial imaging analyses. Altogether, we create a unified atlas of human atherosclerosis informing cell state-specific mechanistic and translational studies of cardiovascular diseases.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 02 May 2024 06:34
Last Modified: 02 May 2024 06:34

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