TY - JOUR
T1 - Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis
AU - Mosquera, Jose Verdezoto
AU - Auguste, Gaëlle
AU - Wong, Doris
AU - Turner, Adam W
AU - Hodonsky, Chani J
AU - Alvarez-Yela, Astrid Catalina
AU - Song, Yipei
AU - Cheng, Qi
AU - Lino Cardenas, Christian L
AU - Theofilatos, Konstantinos
AU - Bos, Maxime
AU - Kavousi, Maryam
AU - Peyser, Patricia A
AU - Mayr, Manuel
AU - Kovacic, Jason C
AU - Björkegren, Johan L M
AU - Malhotra, Rajeev
AU - Stukenberg, P Todd
AU - Finn, Aloke V
AU - van der Laan, Sander W
AU - Zang, Chongzhi
AU - Sheffield, Nathan C
AU - Miller, Clint L
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/11/28
Y1 - 2023/11/28
N2 - 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.
AB - 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.
KW - Atherosclerosis/genetics
KW - Calcium-Binding Proteins/genetics
KW - Coronary Artery Disease/genetics
KW - Genome-Wide Association Study
KW - Humans
KW - Myocardial Infarction
KW - Myocytes, Smooth Muscle
KW - Plaque, Atherosclerotic
UR - http://www.scopus.com/inward/record.url?scp=85176251556&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2023.113380
DO - 10.1016/j.celrep.2023.113380
M3 - Article
C2 - 37950869
SN - 2211-1247
VL - 42
JO - Cell Reports
JF - Cell Reports
IS - 11
M1 - 113380
ER -