Single-cell RNA sequencing reveals the diversity and biology of valve cells in cardiac valve disease.

From highly aligned extracellular fibrils to the cells, a multilevel ordered hierarchy in valve leaflets is crucial for their biological function. Cardiac valve pathology most frequently involves a disruption in normal structure-function correlations through abnormal and complex interaction of cells, extracellular matrix, and their environment. At present, effective treatment for valve disease is limited and frequently ends with surgical repair or replacement with a mechanical or artificial biological cardiac valve, which comes with insuperable complications for many high-risk patients including aged and pediatric populations. Therefore, there is a critical need to fully appreciate the pathobiology of valve disease in order to develop better, alternative therapies. To date, the majority of studies have focused on delineating valve disease mechanisms at the cellular level. However, the cellular heterogeneity and function is still unclear. In this review, we summarize the body of work on valve cells, with a particular focus on the discoveries about valve cells heterogeneity and functions using single-cell RNA sequencing. We conclude by discussing state-of-the-art strategies for deciphering heterogeneity of these complex cell types, and argue this knowledge could translate into the improved personalized treatment of cardiac valve disease.