GSE194180
Single cell RNA sequencing of valvular interstitial cells and adipose derived mesenchymal stem cells
A disease driver population within interstitial cells of human calcific aortic valves identified via single-cell and proteomic profiling Cellular heterogeneity of aortic valves complicates mechanistic evaluation of the calcification processes in calcific aortic valve disease (CAVD), and animal disease models are lacking. In this study, we identify a disease driver population (DDP) within valvular interstitial cells (VICs). Through stepwise single-cell analysis, phenotype-guided  -OMIC profiling, and network-based analysis, we characterize  DDP fingerprint as CD44highCD29+CD59+CD73+CD45low and discover potential key regulators of human CAVD. These DDP-VICs demonstrate multi-lineage differentiation and osteogenic properties. Temporal proteomic profiling of DDP-VICs identifies potential targets for therapy, including MAOA and CTHRC1. In vitro loss-of-function experiments confirm our targets. Such a stepwise strategy may be advantageous for therapeutic target discovery in other disease contexts. Overall design: Unsorted and FACS sorted VICs together with MSCs (reference cell line) were cultured in either normal or osteogenic media for two weeks then processed for single cell RNAseq using InDrops platform.  Sequencing is done on a NextSeq (single read)