Vascular smooth muscle cell state trajectories mediate molecular mechanisms of coronary disease risk - PubMed
3 hours ago
- #single-cell transcriptomics
- #vascular smooth muscle cells
- #coronary artery disease
- Vascular smooth muscle cells (VSMCs) contribute to heritable coronary artery disease (CAD) risk and undergo complex transitions to disease-related phenotypes.
- A dense time-course single-cell transcriptomic and epigenetic map of atherosclerosis in a murine model was developed, accompanied by high-plex in situ spatial data.
- Key transcription factors driving cell state changes were identified using temporal data and probabilistic fate modeling, including network-based prioritization and in silico transcription factor perturbation.
- Knockout studies of the CAD gene Tcf21 revealed its role in regulating VSMC transition, particularly in the secondary heart field.
- Integration of murine atlas data with human CAD genetics identified VSMC phenotypes mediating disease risk, highlighting causal mechanisms.
- The study provides single-cell resolution insights into atherosclerosis trajectories and identifies genetic, transcriptomic, and epigenomic mechanisms of CAD risk.