Figure and Table | Recent Advances in Single-Cell Analysis of Atherosclerotic Plaque Biology

Table 1. Summary of Single-Cell and Spatial Transcriptomic Studies on Atherosclerotic Plaques.

From: Recent Advances in Single-Cell Analysis of Atherosclerotic Plaque Biology

Authors (year)	Samples (species, tissue)	Method	Key findings
Winkels et al. (2018) ⁽⁹⁾	Mouse (Apoe^−/−, Ldlr^−/− aortic plaques)	scRNA-seq	Established an immune cell atlas of atherosclerotic aortas, identifying 11 distinct leukocyte clusters in Apoe^−/− and Ldlr^−/− mice.
Cochain et al. (2018) ⁽¹⁰⁾	Mouse (Ldlr^-/- model: normal vs. high-fat diet aortic plaques)	scRNA-seq	Identified 13 immune cell clusters, including inflammatory macrophages (Il1b^high) and Trem2^high lipid-associated macrophages.
Wirka et al. (2019) ⁽¹¹⁾	Mouse (Apoe^-/- aortic plaques with SMC-Tcf21 knockout); human coronary arteries from explanted transplant hearts	scRNA-seq + SMC lineage tracing	Showed that SMCs do not transdifferentiate into macrophages but instead transition into fibroblast-like “fibromyocytes”. Higher TCF21 expression correlated with greater fibromyocyte presence and reduced CAD risk, confirming TCF21 promotes SMC phenotypic modulation in atheroprotection.
Fernandez et al. (2019) ⁽¹²⁾	Human carotid plaques (patients with symptoms vs. those without)	scRNA-seq + CITE-seq	Symptomatic plaques contained activated CD4⁺ T cell subsets (high PD-1 expression) and alternative macrophages linked to plaque vulnerability, whereas asymptomatic plaques showed IL-1β pathway immune activation.
Alencar et al. (2020) ⁽¹³⁾	Human carotid plaques; mouse (Apoe^-/- plaques with SMC/EC lineage tracing)	scRNA-seq + dual-lineage tracing	Identified Lgals3⁺ pioneer cells, which transition into osteogenic states in advanced plaques. Knockout of Klf4 blocked this transition, indicating that it plays a key role in late-stage plaque pathogenesis.
Pan et al. (2020) ⁽¹⁴⁾	Mouse (Ldlr^-/- SMC lineage-traced aortic plaques) + human plaques	scRNA-seq + lineage tracing	Discovered stem-endothelial-monocyte-like multipotent cells in atherosclerotic plaques, capable of differentiating into macrophage-like or fibrochondrocyte-like cells. Identified retinoic acid signaling as a key regulator, which, when pharmacologically activated, reduced plaque burden and stabilized the fibrous cap.
Depuydt et al. (2020) ⁽¹⁵⁾	Human carotid endarterectomy plaques	scRNA-seq + scATAC-seq	Identified 14 distinct cell clusters, highlighting immune cell heterogeneity. Integrated chromatin accessibility data revealed transcription factor networks driving cell state transitions and spatial microanatomy within plaques.
Newman et al. (2021) ⁽¹⁶⁾	Mouse (Apoe^-/- brachiocephalic plaques, SMC-Pdgfrb knockout) and human plaques	scRNA-seq + lineage tracing	Found that fibrous cap myofibroblasts in plaques are primarily derived from smooth muscle cells, whereas a subset originates from endothelial or macrophage lineages through endothelial-to-mesenchymal transition or macrophage-to-mesenchymal transition.
Cheng et al. (2022) ⁽¹⁷⁾	Mouse (SMC-specific Zeb2 perturbation model); human coronary SMCs	scRNA-seq + scATAC-seq	Identified ZEB2 as the causal gene at a CAD risk locus. Integrated transcriptomic and chromatin accessibility data revealed that ZEB2 regulates SMC phenotypic plasticity through epigenetic remodeling, promoting pro-inflammatory and osteogenic transitions in plaques.
Emoto et al. (2022) ⁽¹⁸⁾	Human coronary culprit plaques (ACS vs CCS patients)	scRNA-seq	Identified distinct immune profiles in ACS plaques, including increased monocytes, mast cells, and inflammatory macrophages with high CXCL3 and IL1B expression, compared with CCS plaques.
Chowdhury et al. (2022) ⁽¹⁹⁾	Human coronary plaques	scRNA-seq + scTCR-seq	Identified clonally expanded CD8⁺ T cells in plaques with TCRs reactive to viral peptides that mimic self-antigens. Revealed cross-reactivity between viral and arterial peptides, suggesting molecular mimicry as a mechanism of T cell-driven vascular inflammation.
Wang et al. (2023) ⁽²⁰⁾	Mouse (Apoe^-/^- aorta with HFD); human carotid plaques	scRNA-seq + scTCR-seq	Showed breakdown of T cell tolerance checkpoints in atherosclerosis. Clonally expanded T cells in plaques showed enrichment for PDCD1, CTLA4, and pro-inflammatory genes, suggesting sustained antigenic stimulation.
Depuydt et al. (2023) ⁽²¹⁾	Human carotid plaques and paired blood	scRNA-seq + scTCR-seq	Revealed clonally expanded CD4⁺ effector memory T cells enriched in plaques with autoimmune-like transcriptional signatures. Identified CD69⁺FOS⁺ T cells indicative of recent TCR stimulation and tissue residency.
Sun et al. (2023) ⁽²²⁾	Human carotid plaques	Spatial transcriptomics	Identified distinct transcriptional signatures in plaque areas prone to rupture, providing spatial insights into plaque vulnerability.
Tan et al. (2023) ⁽²³⁾	Human carotid plaques and paired blood samples	scRNA-seq	Constructed a single-cell atlas of carotid atherosclerosis, identifying immune and endothelial subsets associated with cerebrovascular events. Highlighted pro-inflammatory T cell subsets and monocyte/macrophage states enriched in symptomatic plaques, linking immune heterogeneity to plaque vulnerability.
Mori et al. (2024) ⁽²⁴⁾	Human carotid plaques	scRNA-seq	CD163⁺ macrophages trigger NF-κB-dependent EndMT within the fibrous cap; CD163 deletion attenuated EndMT and plaque growth, and an EndMT cluster enriched for apoptosis genes was identified by single-cell profiling.
Bashore et al. (2024) ⁽²⁵⁾	Human carotid plaques	scRNA-seq + CITE-seq	Identified multiple cell populations and their subtypes in human plaques. Enhanced understanding of cell heterogeneity and interactions, informing mechanisms underlying plaque progression.
Gastanadui et al. (2024) ⁽²⁶⁾	Human coronary plaques	Spatial transcriptomics	Revealed that inflammatory gene expression profiles differed between stable and unstable coronary plaques, highlighting spatially resolved mechanisms of plaque stability.
Bleckwehl et al. (2025) ⁽²⁷⁾	Human coronary and carotid atherosclerotic plaques (various stages)	Spatial transcriptomics + scRNA-seq	Created a spatial transcriptomic atlas of atherosclerotic plaques, revealing that microvascular remodeling is linked to immune cell recruitment and plaque progression. Identified specific immune-microvascular niches as potential therapeutic targets for plaque stabilization.
Lai et al. (2025) ⁽²⁸⁾	Human carotid endarterectomy plaques; paired perivascular adipose tissue and blood	Spatial transcriptomics + scRNA-seq	Identified tertiary lymphoid-organ-like niches marked by fibroblast-like SMCs expressing CXCL12, CCL19, and VCAM1; these niches recruit lymphocytes and are independently associated with symptomatic carotid disease.

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