Table.
Marker genes associated with SMC phenotypic transitionsa
| Cell type | Gene marker | Experimental design |
|---|---|---|
| Macrophage-like/phagocytic cells | ||
| Mouse studies | ||
| Cd74, yz2, C1qa, C1qb, H2-Aa, H2-Ab1, C1qC, H2-Eb1 | SMC-derived cells in macrophage cell cluster by scRNA sequencing with SMC-lineage tracing of ApoE−/-− mice38 | |
| Itgam, Mrc1, Adgre1, Ptprc, Cd68, Lgals3 | SMC-derived cells in macrophage cell cluster by scRNA sequencing with SMC-lineage tracing of ApoE−/− mice39 | |
| CD68, Lyz2, Fcer1g | SMC-derived cells in macrophage cell clusters by scRNA sequencing with SMC-lineage tracing of ApoE−/− mice21 | |
| Lgals3, CD68 | Immunofluorescent staining in vivo; oxidized low-density lipoprotein staining and morphologic analysis by electron microscopy35 | |
| Human studies | ||
| CD68 | Immunofluorescent staining in vivo; phagocytosis assay in vitro with cholesterol loading22 | |
| ACTA2, CD68, Abca1 | Immunofluorescent staining42 | |
| In vitro studies | ||
| Mac2, CD68, Abca1 | In vitro cholesterol loading; phagocytosis assay in vitro10,43 | |
| MSC-like cells | ||
| Mouse studies | ||
| Ly6a/Sca1 | scRNA sequencing with SMC-lineage tracing of ApoE−/− mice; immunofluorescent staining in vivo21 | |
| Sca1 | Immunofluorescent staining in vivo22 | |
| Sca1, Lgals3, Vcam1 | SMC-derived transitioning cluster by scRNA sequencing with SMC lineage tracing of ApoE−/− mice; Lgals3 SMC dual lineage tracing validation39 | |
| Human studies | ||
| Human homolog Sca1 has not been identified | ||
| Osteochondrogenic/chondrocyte-like cells | ||
| Mouse studies | ||
| Runx2, RANKL | Runx2-deficient mice consuming high-fat diet showed decreased vascular calcification in vivo44 | |
| Sox9, Ibsp, Chad | SMC-derived cells present in chondrocyte cell cluster by scRNA sequencing with SMC lineage tracing of ApoE−/− mice21 | |
| Sox9, Runx2, Cytl1, Ibsp, Alpl | SMC-derived osteogenic cluster by scRNA sequencing with SMC-lineage tracing mice; Sox9 staining on mouse plaque39 | |
| Human studies | ||
| TRPV4, S100 B, Sox9 | Validation in ruptured human coronary atherosclerotic lesions39 | |
| In vitro studies | ||
| PiT-1, Dmp1, E11, SOST | In vitro calcification, as measured by Alizarin red staining and alkaline phosphatase activity48 | |
| Runx2, BMP-2 | Hypoxic conditions and HiPO4 treatment drove increased mineralization of SMCs45 | |
| ALPL, Runx2, MGP, COL1A2 | Alkaline phosphatase activity and deposition of calcified matrix in vitro46 | |
| Sox9, Agg, Col II, TG2 | In vitro chondrogenesis of SMCs47 | |
| Fibromyocyte | ||
| Mouse studies | ||
| Lgals3, Tnfrsf11b, TCF21, Lum, Dcn, Bgn, Mgp | SMC-derived fibromyocyte cluster by scRNA sequencing with SMC lineage tracing of ApoE−/− mice; in situ hybridization for Lum mRNA on mouse fibrous cap; TCF21 SMC-specific knockout reduced SMC contribution to fibrous cap by SMC-lineage tracing38 | |
| Human studies | ||
| TCF21, Tnfrsf11b, Mgp, Bgn, Lum, MMP2, Dcn | Human atherosclerotic coronary arteries scRNA sequencing; in situ hybridization of Tnfrsf11b mRNA within human coronary lesion38 |
MSC, Mesenchymal stem cell; scRNA, small conditional RNA; SMC, smooth muscle cell.
a
Some markers such as Sox9 seem specific to the osteochondrogenic transition; however, others such as Lgals3 appear to not be expressed by different SMC subpopulations.