Table 1. Heterogeneity among vascular cell populations as defined by scRNA-seq.
| S.No | Health status | Species | Vascular compartment | ECs | VSMCs | Mφ | Fib | Description/Main findings |
|---|---|---|---|---|---|---|---|---|
| 1 | Healthy | mouse | Whole aorta | 3 | 1 | 1 | 2 | Most significant heterogeneity was observed in ECs. The two major EC subpopulations (Vcam1+/Cd36− and Vcam1−/Cd36+) showed unique distribution pattern in the lesser and greater curvatures that may be the result of differences in blood flow and shear stress [24]. |
| 2 | Healthy | Mouse (C57BL/6) | Endothelium of descending aorta | 2 | - | - | - | scRNA-seq analysis of CD34+ (isolated via FACs) cells revealed two distinct aortic endothelial populations. The authors suggested that the progenitor cells (Pdgfr, Sox9, Il33, Postn, Dcn) transition to differentiated cells [23]. |
| 3 | Atherosclerotic | Mouse (Ldlr−/−) | CD45+ aortic cells | - | - | 3 | - | ScRNA-seq analysis of CD45+ cells identified 13 leukocytes’ populations with three major Mφ populations including two atherosclerosis-specific population that are inflammatory and foamy Trem2hi Mφ [18]. |
| 4 | Atherosclerotic | Mouse (Apoe−/−) | CD45+ aortic cells (thoracic and abdominal) | - | - | 1 | - | ScRNA-seq analysis of CD45+ cells identified 11 leukocytes’ populations including three B-cell subsets. The results were confirmed by CYTOF as a second method [19]. |
| 5 | Atherosclerotic | Human | CD45+ cells of carotid artery plaques | - | - | 2 | Single cell proteomic (CyTOF) and transcriptomic (CITE-seq and scRNA-seq) of plaque and blood from same patients unraveled distinct feature of both T cells and macrophages in symptomatic and asymptomatic disease [182]. | |
| 6 | Atherosclerotic | Mouse (Ldlr−/−) | CD45+ aortic cells | - | - | 2 | - | ScRNA-seq analysis of CD45+ cells identified 11 leukocytes. Macrophages were the largest population. Inflammatory genes were down-regulated in foamy macrophages whereas intimal non-foamy macrophages showed a distinct inflammatory phenotype [20]. |
| 7 | Atherosclerotic | human | Carotid artery plaques | 2 | 2 | 3 | This is the first study that also covers non-immune cells in human plaque. In total, 14 cell populations were identified with 11 leukocytes and 3 non-immune cellular clusters. Transcriptional data of endothelial subpopulations are suggestive of an activated and a transitory to mesenchymal phenotype. SMCs showed a contractile and synthetic phenotype. One B cell and four T cell clusters were also identified. Mφ included two pro-inflammatory Mφ and a foamy Trem2hi Mφ populations [25]. | |
| 8 | Atherosclerotic | Mouse (Ldlr−/−) | CD11+ CX3CR1+ monocyte lineage aortic arch cells | - | - | 3 | - | ScRNA-seq analysis combined with genetic fate mapping profiled plaque cells derived from CX3CR1 precursors in plaque during progression and regression of atherosclerosis. The present study tracks the cellular state during the differentiation of CXC3R1 cells into macrophages in atherosclerosis. Eleven cellular clusters were identified including three macrophages identified by Cochain et al. confirming the heterogeneity of macrophages. They also identified a proliferating monocyte cluster with a stem-like phenotype [183]. |
| 9 | Atherosclerotic | Mouse (Apoe−/−) | Aortic leukocytes | - | - | 2 | - | ScRNA-seq analysis of aortic leukocytes after macrophage-specific nano-therapy using single-walled carbon nanotubes (SWNT). The data revealed that pro-phagocytic SWNT decreased inflammatory phenotype in macrophages [184]. |
| 10 | Atherosclerotic | Mouse (Ldlr−/-, Apoe−/−) and human | Mouse (Ascending and thoracic aorta and brachiocephalic artery) and human (carotid plaques) | 2 | 3 | 3 | 2 | ScRNA-seq in SMC-lineage tracing mice identified multiple SMC-derived cell state during atherosclerosis. SMC may transition through an intermediate cell state (termed as SEM cells by the authors) to multiple cell types [26]. |
| 11 | Healthy and atherosclerotic | Mouse (C57BL/6and Apoe−/−) | medial cells aortic arch and thoracic aorta | - | 3 | - | - | ScRNA-seq combined with SMC-lineage tracing identified a rare population of multipotent progenitor marker Sca1+ VSMCs which was shown to be a hallmark of VSMC transition from contractile to inflammatory phenotype [107]. |
| 12 | Atherosclerotic | Mouse (Apoe−/−) and human | Aortic root in mice and right coronary artery in human | 3(m) 1(h) | 3(m) 2(h) | 1(m) 1(h) | 2(m) 2(h) | scRNA-seq combined with SMC-lineage tracing identified a transition of SMC to fibroblast-like cells which were also present in human plaques [108]. |
| 13 | Atherosclerotic | Mouse (Apoe−/−) | Adventitia of the whole aorta | 1 | 1 | 2 | 4 | This scRNA-seq atlas of aortic adventitia characterized resident and bone marrow-derived cell populations with identification of mesenchyme cells expression stem/progenitor markers that could be a source to several differentiated cells [131]. |
Abbreviations: EC, endothelial cell; Fib’, fibroblasts; h, human; m, mouse; Mφ, macrophage.