Embryonic stem cell differentiation models: cardiogenesis, myogenesis, neurogenesis, epithelial and vascular smooth muscle cell differentiation in vitro

Embryonic stem cells, totipotent cells of the early mouse embryo, were esta blished as permanent cell lines of undifferentiated cells. ES cells provide an important cellular system in developmental biology for the manipulation of preselected genes in mice by using the gene targeting technology. Embry onic stem cells, when cultivated as embryo-like aggregates, so-called `embr yoid bodies', are able to differentiate in vitro into derivatives of all th ree primary germ layers, the endoderm, ectoderm and mesoderm. We establishe d differentiation protocols for the in vitro development of undifferentiate d embryonic stem cells into differentiated cardiomyocytes, skeletal muscle, neuronal, epithelial and vascular smooth muscle cells. During differentiat ion, tissue-specific genes, proteins, ion channels, receptors and action po tentials were expressed in a developmentally controlled pattern. This patte rn closely recapitulates the developmental pattern during embryogenesis in the living organism. In vitro, the controlled developmental pattern was fou nd to be influenced by differentiation and growth factor molecules or by xe nobiotics. Furthermore, the differentiation system has been used for geneti c analyses by `gain of function' and `loss of function' approaches in vitro .