Embryonic stem (ES) cells, derived from the inner cell mass of blastocyst-stage embryos, are pluripotent cells capable of generating all cell types in the body. They have been instrumental in advancing biology and medicine, enabling the manipulation of the mouse genome and the development of in vitro models of early mammalian development. ES cells have also been considered a potential source of cells for cell replacement therapy. Recent advances in understanding ES cell differentiation have provided new insights for developing ES cell-based developmental models and generating clinically relevant populations for cell therapy. ES cells can be maintained as undifferentiated cells in culture, retaining normal karyotypes, and are pluripotent, capable of generating all cell types. The pluripotent nature of mouse ES cells was demonstrated by their ability to contribute to all tissues of adult mice. ES cells can differentiate into various cell types in culture, including those from the three embryonic germ layers. The ability to derive multiple lineages from ES cells opens new opportunities to model embryonic development in vitro for studying the events regulating the earliest stages of lineage induction and specification. ES cell differentiation has been used to generate a broad spectrum of cell types, including hematopoietic, vascular, cardiac, and mesodermal lineages. Hematopoietic development in ES cells has been studied extensively, with findings showing that ES cell differentiation models closely mimic the early embryo. Hematopoietic commitment in ES cells can be monitored by gene expression patterns, cell surface markers, and the development of clonable progenitor cells. The development of hematopoietic lineages in ES cells has been shown to recapitulate the developmental program observed in the early embryo. The hemangioblast hypothesis, which suggests that hematopoietic and endothelial lineages develop from a common progenitor, has been supported by studies using the ES cell differentiation model. The ES cell differentiation system has also been instrumental in characterizing the earliest stages of hematopoietic development, revealing dynamic changes in the expression of cell surface proteins. The ES cell system has been used to investigate the regulation of hematopoietic commitment and to generate large numbers of cells from specific hematopoietic lineages for molecular and biochemical analyses as well as for transplantation for short-term lineage replacement therapy. The development of the cardiac lineage in ES cell differentiation cultures is easily detected by the appearance of areas of contracting cells that display characteristics of cardiomyocytes. The development of the cardiomyocyte lineage has been analyzed in detail, with the expression of cardiac genes and the maturation of the lineage in the cultures associated with changes in cell size and shape. The development of the cardiac lineage in ES cell cultures has been shown to be regulated by various factors, including EGF-CFC factor Cripto, Notch signaling, BMP2, FGF2, nitric oxide, and ascorbic acid. The transplantation of ES-cell-derived cardiomyocytes has shown promise for the treatment of cardiovascularEmbryonic stem (ES) cells, derived from the inner cell mass of blastocyst-stage embryos, are pluripotent cells capable of generating all cell types in the body. They have been instrumental in advancing biology and medicine, enabling the manipulation of the mouse genome and the development of in vitro models of early mammalian development. ES cells have also been considered a potential source of cells for cell replacement therapy. Recent advances in understanding ES cell differentiation have provided new insights for developing ES cell-based developmental models and generating clinically relevant populations for cell therapy. ES cells can be maintained as undifferentiated cells in culture, retaining normal karyotypes, and are pluripotent, capable of generating all cell types. The pluripotent nature of mouse ES cells was demonstrated by their ability to contribute to all tissues of adult mice. ES cells can differentiate into various cell types in culture, including those from the three embryonic germ layers. The ability to derive multiple lineages from ES cells opens new opportunities to model embryonic development in vitro for studying the events regulating the earliest stages of lineage induction and specification. ES cell differentiation has been used to generate a broad spectrum of cell types, including hematopoietic, vascular, cardiac, and mesodermal lineages. Hematopoietic development in ES cells has been studied extensively, with findings showing that ES cell differentiation models closely mimic the early embryo. Hematopoietic commitment in ES cells can be monitored by gene expression patterns, cell surface markers, and the development of clonable progenitor cells. The development of hematopoietic lineages in ES cells has been shown to recapitulate the developmental program observed in the early embryo. The hemangioblast hypothesis, which suggests that hematopoietic and endothelial lineages develop from a common progenitor, has been supported by studies using the ES cell differentiation model. The ES cell differentiation system has also been instrumental in characterizing the earliest stages of hematopoietic development, revealing dynamic changes in the expression of cell surface proteins. The ES cell system has been used to investigate the regulation of hematopoietic commitment and to generate large numbers of cells from specific hematopoietic lineages for molecular and biochemical analyses as well as for transplantation for short-term lineage replacement therapy. The development of the cardiac lineage in ES cell differentiation cultures is easily detected by the appearance of areas of contracting cells that display characteristics of cardiomyocytes. The development of the cardiomyocyte lineage has been analyzed in detail, with the expression of cardiac genes and the maturation of the lineage in the cultures associated with changes in cell size and shape. The development of the cardiac lineage in ES cell cultures has been shown to be regulated by various factors, including EGF-CFC factor Cripto, Notch signaling, BMP2, FGF2, nitric oxide, and ascorbic acid. The transplantation of ES-cell-derived cardiomyocytes has shown promise for the treatment of cardiovascular