Side- and disease-dependent changes in human aortic valve cell population and transcriptomic heterogeneity determined by single-cell RNA sequencing

Calcific aortic valve disease develops preferentially on the fibrosa side while the ventricularis side remains relatively spared with unknown mechanisms. We hypothesized that the fibrosa is prone to the disease due to side-dependent differences in transcriptomic patterns and cell phenotypes. To test this hypothesis, we performed single-cell RNA-sequencing using a new method to collect endothelial-enriched samples from either the fibrosa or ventricularis of freshly-obtained human AV leaflets from 5 donors ranging from non-diseased to fibrocalcific stages. Overall design: Human aortic valve cells, including valvular endothelial cells (VEC), valvular interstitial cells (VIC), immune cells (macrophages, t-cells), transitional cells, and stromal cells from 5 donors ranging from non-diseased to fibrocalcific