Hematopoietic colony-forming cells derived from human embryonic stem cells

Human embryonic stem (ES) cells are undifferentiated, pluripotent cells tha t can be maintained indefinitely in culture. Here we demonstrate that human ES cells differentiate to hematopoietic precursor cells when cocultured wi th the murine bone marrow cell line S17 or the yolk sac endothelial cell li ne C166. This hematopoietic differentiation requires fetal bovine serum, bu t no other exogenous cytokines. ES cell-derived hematopoietic precursor cel ls express the cell surface antigen CD34 and the hematopoietic transcriptio n factors TAL-1, LMO-2, and GATA-2. When cultured on semisolid media with h ematopoietic growth factors, these hematopoietic precursor cells form chara cteristic myeloid, erythroid, and megakaryocyte colonies. Selection for CD3 4(+) cells derived from human ES cells enriches for hematopoietic colony-fo rming cells, similar to CD34 selection of primary hematopoietic tissue (bon e marrow, umbilical cord blood). More terminally differentiated hematopoiet ic cells derived from human ES cells under these conditions also express no rmal surface antigens: glycophorin A on erythroid cells, CD15 on myeloid ce lls, and CD41 on megakaryocytes. The in vitro differentiation of human ES c ells provides an opportunity to better understand human hematopoiesis and c ould lead to a novel source of cells for transfusion and transplantation th erapies.