Hemogenic endothelium can be modeled with in vitro differentiation of human embryonic stem cells. Hemogenic endothelial can be modeled within novel MHE colonies from in vitro differentiated hEB cells under serum-free conditions with hematopoietic growth factors (A). Mesodermal-hemato-endothelial colonies from day 6 to 10 hEB cells first adhere to plastic dishes, then expand laterally, and eventually bud off multipotent, or hemoglobinizing erythroblastic hematopoietic cells (right panels). The adherent portion of MHE colonies (left panel) has been demonstrated to be a mixture of mesenchymal cells and mature endothelial cells capable of taking up acetylated low-density lipoprotein. Our main hypothesis, as described in the text, (B) puts in parallel, in a schematic way, the sequence of appearance of key markers of hematopoiesis/angiogenesis left) and the order of emergence of angio-hematopoietic/hematopoietic progenitor cells (right) in our hES/hEB differentiation system. We propose that mesoderm commitment to hemangioblastic precursors from hESC is correlated directly with the emergence of CD34, CD31, SCL/TAL1, and CDX4 expression in hEB cells. Reprinted with permission from Zambidis ET, Peault B, Park TS, Bunz F, and Civin C. Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development.