Mature cardiomyocytes from human pluripotent stem cells for drug screening and disease modeling

Abstract

Differentiation of human pluripotent stem cells (hPSCs) to the cardiac lineage represents a potentially unlimited source of cardiomyocytes (CMs) for research and clinical applications. Limitations to their use include their immature, embryonic-like developmental state and their heterogeneity characterized by mixed population of cells and poorly defined function. Using a unique strategy for proteomics profiling, we identified proteins on the cell surface of hPSCCMs. Our dataset revealed an association between the expression of late protein 1 (L1), a surface protein involved in metabolism, with a more advanced differentiation stage, Viable CMs positive for this developmental marker can be isolated by cell sorting and are more adult-like in their gene expression pattern, morphology and functions. Our work provides important proof-ofprinciple for the isolation and characterisation of mature and defined hPSCCM subpopulations, and will greatly advance the use of hESC-derivatives for medical research, disease modelling and drug testing.