EMBRYONIC STEM CELL-DERIVED CARDIAC DIFFERENTIATION - MODULATION OF DIFFERENTIATION AND LOSS-OF-FUNCTION ANALYSIS IN-VITRO

Mouse embryonic stem (ES) cells, when cultivated as embryo-like aggreg ates, are able to differentiate in vitro into derivatives of all prima ry germ layers. These include functionally active cardiomyocytes repre senting ventricle-like, atrium-like, and pacemaker-like cells. During differentiation, a developmentally controlled expression pattern of ca rdiac-specific genes, proteins, action potentials, ion channels, and r eceptors is found. This developmental pattern can be modulated in vitr o by differentiation factors such as retinoic acid or by ''gain-of-fun ction'' and ''loss-of-function'' approaches. The latter strategy was s uccessfully used for the characterization of cardiac phenotypes of bet a(1) integrin-deficient ES cells after differentiation into the cardio genic lineage. (C) 1998, Elsevier Science Inc.