학술논문
Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis
Document Type
article
Author
Jose Verdezoto Mosquera; Gaëlle Auguste; Doris Wong; Adam W. Turner; Chani J. Hodonsky; Astrid Catalina Alvarez-Yela; Yipei Song; Qi Cheng; Christian L. Lino Cardenas; Konstantinos Theofilatos; Maxime Bos; Maryam Kavousi; Patricia A. Peyser; Manuel Mayr; Jason C. Kovacic; Johan L.M. Björkegren; Rajeev Malhotra; P. Todd Stukenberg; Aloke V. Finn; Sander W. van der Laan; Chongzhi Zang; Nathan C. Sheffield; Clint L. Miller
Source
Cell Reports, Vol 42, Iss 11, Pp 113380- (2023)
Subject
Language
English
ISSN
2211-1247
Abstract
Summary: 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.