Embryonic stem (ES) cells efficiently differentiate in vitro to mesoderm and hematopoietic cells, recapitulating days 6.5 to 7.5 of mouse hematopoietic development. Differentiated ES cells form embryoid bodies (EBs), which develop erythroid precursors by day 4 and more than 85% of EBs contain such cells by day 6. Gene expression profiles show that primitive endoderm and mesoderm markers are present in EBs and embryos before hematopoiesis begins. GATA-1, GATA-3, and vav are expressed in EBs and embryos prior to hematopoiesis, suggesting roles in early hematopoietic development. Hematopoietic development in EBs occurs without added growth factors and is not significantly influenced by factors like IL-3, IL-1, IL-6, IL-11, erythropoietin, and Kit ligand. By days 10 and 14, EB hematopoiesis is enhanced by Kit ligand and IL-11. Kinetic analysis shows a sequential development of hematopoietic precursors, with primitive erythroid precursors appearing first, followed by bipotential neutrophil/macrophage and multilineage precursors, and mast cell precursors last. This pattern mirrors that in the yolk sac and early fetal liver, indicating that in vitro hematopoiesis parallels in vivo development. The mouse hematopoietic system is established early from the yolk sac's extraembryonic mesoderm. The first visible hematopoietic activity occurs at 7.5-8.0 days of gestation in the yolk sac blood islands, which consist of erythroid-committed cells. Precursors of these cells develop before blood island hematopoiesis. Hematopoietic development in mice is characterized by rapid changes, with no signs of hematopoiesis at 7.5 days but numerous blood islands by day 8. The yolk sac remains the primary hematopoietic organ until day 12, after which the fetal liver becomes predominant. The mechanisms of hematopoietic development and growth factor regulation are not fully understood. At the molecular level, genes like GATA family members, c-myb, and SCL are involved in early hematopoietic commitment. GATA-1 is essential for erythroid development, while c-myb is essential for fetal but not embryonic hematopoiesis. SCL is expressed in hematopoietic cells. Vav is expressed in the fetal liver and may be involved in early hematopoiesis. In vitro models using ES cells allow study of hematopoietic development without the limitations of early embryos. ES cells can be differentiated in culture to generate hematopoietic cells with a reproducible kinetic pattern. Gene expression profiles in EBEmbryonic stem (ES) cells efficiently differentiate in vitro to mesoderm and hematopoietic cells, recapitulating days 6.5 to 7.5 of mouse hematopoietic development. Differentiated ES cells form embryoid bodies (EBs), which develop erythroid precursors by day 4 and more than 85% of EBs contain such cells by day 6. Gene expression profiles show that primitive endoderm and mesoderm markers are present in EBs and embryos before hematopoiesis begins. GATA-1, GATA-3, and vav are expressed in EBs and embryos prior to hematopoiesis, suggesting roles in early hematopoietic development. Hematopoietic development in EBs occurs without added growth factors and is not significantly influenced by factors like IL-3, IL-1, IL-6, IL-11, erythropoietin, and Kit ligand. By days 10 and 14, EB hematopoiesis is enhanced by Kit ligand and IL-11. Kinetic analysis shows a sequential development of hematopoietic precursors, with primitive erythroid precursors appearing first, followed by bipotential neutrophil/macrophage and multilineage precursors, and mast cell precursors last. This pattern mirrors that in the yolk sac and early fetal liver, indicating that in vitro hematopoiesis parallels in vivo development. The mouse hematopoietic system is established early from the yolk sac's extraembryonic mesoderm. The first visible hematopoietic activity occurs at 7.5-8.0 days of gestation in the yolk sac blood islands, which consist of erythroid-committed cells. Precursors of these cells develop before blood island hematopoiesis. Hematopoietic development in mice is characterized by rapid changes, with no signs of hematopoiesis at 7.5 days but numerous blood islands by day 8. The yolk sac remains the primary hematopoietic organ until day 12, after which the fetal liver becomes predominant. The mechanisms of hematopoietic development and growth factor regulation are not fully understood. At the molecular level, genes like GATA family members, c-myb, and SCL are involved in early hematopoietic commitment. GATA-1 is essential for erythroid development, while c-myb is essential for fetal but not embryonic hematopoiesis. SCL is expressed in hematopoietic cells. Vav is expressed in the fetal liver and may be involved in early hematopoiesis. In vitro models using ES cells allow study of hematopoietic development without the limitations of early embryos. ES cells can be differentiated in culture to generate hematopoietic cells with a reproducible kinetic pattern. Gene expression profiles in EB