Embryonic stem cells provide a powerful and versatile model system.

Embryonic stem (ES) cells are pluripotent stem cells that differentiate both in vitro and in vivo into cell types derived from each of the three embryonic germ layers. ES cells and their close relatives, embryonal carcinoma (EC) cells and embryonic germ (EG) cells, have been used extensively as model systems for studying early mammalian development. This work has led to important insights into the mechanisms that control embryogenesis at the molecular and cellular levels. This chapter focuses on the use of ES cells as an in vitro model system for studying cellular differentiation and reviews several areas where important progress has been made. Impressive progress has been made in the isolation and characterization of ES cells from many species, including humans. Significant progress has also been made in the development of culture conditions that help direct the differentiation of ES cells to specific cell types that form during myogenesis, angiogenesis, hematopoiesis, neurogenesis, and cardiogenesis. The ability to inactivate virtually any gene in ES cells by gene targeting has vastly improved our understanding of the roles played by specific genes at the cellular and organismic levels. Moreover, ES cells and EC cells have been used widely to investigate how specific genes are turned on and turned off in the course of differentiation. In this connection, DNA array technology has been used to identify genes regulated when ES cells differentiate. The final section of this chapter discusses how work with ES cells is shaping our understanding of stem cells, mammalian development, and cell replacement therapy.