It is well recognized from adult stem cell studies that the growth of transplanted bone marrow is generated from the hematopoietic (“blood-forming”) stem and progenitor cells provided by the donor bone marrow. Mature, differentiated cells that accompany the hematopoietic stem cells, disappear rapidly after transplantation as they lack the ability to self-renew. It is thus essential when designing clinical approaches that use tissue derived from human embryonic stem cells (hESC), to specifically target the production of stem and progenitors that will survive, proliferate and differentiate normally after transplantation. We and others have shown that blood cells can be generated from hESC. However, it has become apparent more recently that the types of blood cells that hESC can produce under current conditions are more limited functionally than those found in bone marrow or cord blood. During the funding of this proposal we have compared the expression of genes in cells produced by hESC to those found in umbilical cord blood. These studies found that a gene called LNK is expressed in stem cells from hESC but not from cord blood. During completion of this grant over the past 4 months, we have found that inhibiting the expression of LNK increases the production of blood from hESC, suggesting that this pathway is a promising target for future studies aimed at increasing the production of blood-forming stem cells from hESC. Second, as part of a UCLA collaborative study we have studied six new hESC lines generated at UCLA for their ability to produce blood, blood vessels and more recently cardiac muscle. Third, we have developed a way to give a signal to cord blood stem cells that induces them to make large numbers of red blood cells. The ultimate goals of all these studies is to improve production of hematopoietic cells from hESC to provide an inexhaustible source of matched stem cells for transplantation.