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How Single-Cell Technologies Have Provided New Insights Into Atherosclerosis
Natalia Eberhardt1,2, Chiara Giannarelli1,2,3
1Department of Medicine, Leon H. Charney Division of Cardiology (N.E., C.G.), New York University Grossman School of Medicine, NYU Langone Health' New York.
Insights
Single-cell technologies reveal complex cellular makeup of atherosclerosis, detailing immune cell roles and plaque changes in mouse models and human patients. These advanced methods enhance understanding of cardiovascular disease progression and potential therapeutic targets.
Area of Science:
- Cardiovascular Biology
- Immunology
- Genomics
Background:
- Atherosclerosis involves complex cellular interactions within plaques.
- Understanding cellular heterogeneity is crucial for disease mechanisms.
Purpose of the Study:
- To review how single-cell technologies illuminate atherosclerotic plaque composition.
- To discuss advancements in identifying cellular alterations in atherosclerosis.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq)
- Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq)
- Transposase-accessible chromatin with high-throughput sequencing (ATAC-seq)
- Cytometry by time-of-flight (CyTOF)
Main Results:
- Single-cell studies identified novel cellular heterogeneity in atherosclerotic plaques.
- These technologies revealed distinct immune, endothelial, and smooth muscle cell states.
- Analysis of mouse models showed cellular responses to diet and genetic factors.
Conclusions:
- Single-cell approaches provide unprecedented insight into atherosclerosis.
- They enable mapping of cellular and molecular plaque composition in humans.
- New immune alterations in human plaques, including in stroke patients, have been discovered.
Abstract:
The development of innovative single-cell technologies has allowed the high-dimensional transcriptomic and proteomic profiling of individual blood and tissue cells. Recent single-cell studies revealed a new cellular heterogeneity of atherosclerotic plaque tissue and allowed a better understanding of distinct immune functional states in the context of atherosclerosis. In this brief review, we describe how single-cell technologies have shed a new light on the cellular composition of atherosclerotic plaques, and their response to diet perturbations or genetic manipulation in mouse models of atherosclerosis. We discuss how single-cell RNA sequencing, cellular indexing of transcriptomes and epitopes by sequencing, transposase-accessible chromatin with high-throughput sequencing, and cytometry by time-of-flight platforms have empowered the identification of discrete immune, endothelial, and smooth muscle cell alterations in atherosclerosis progression and regression. Finally, we review how single-cell approaches have allowed mapping the cellular and molecular composition of human atherosclerotic plaques and the discovery of new immune alterations in plaques from patients with stroke.
