Small Molecule-Mediated Directed Differentiation of Human Embryonic Stem Cells Toward Ventricular Cardiomyocytes

摘要: The generation of human ventricular cardiomyocytes from embryonic stem cells and/or induced pluripotent could fulfill the demand for therapeutic applications and in vitro pharmacological research; however, production a homogeneous population remains major limitation. By combining small molecules growth factors, we developed fully chemically defined, directed differentiation system to generate ventricular-like (VCMs) with high efficiency reproducibility. Molecular characterization revealed that recapitulated developmental steps cardiovascular fate specification. Electrophysiological analyses further illustrated highly enriched VCMs. These VCMs exhibited expected cardiac electrophysiological calcium handling properties as well appropriate chronotropic responses cardioactive compounds. In addition, using an integrated computational experimental systems biology approach, demonstrated modulation canonical Wnt pathway by molecule IWR-1 plays key role cardiomyocyte subtype summary, reproducible efficient platform facilitates chemical genetics-based interrogation signaling pathways during cardiogenesis bypasses limitations genetic approaches provides valuable source screenings cell replacement therapies.