Platform described in Rafii et al for differentiation of human embryonic stem cells (ESCs) to hemogenic endothelium (HE) and subsequent waves of hematopoietic progenitor cells using endothelial cell (EC) co-culture. Sequential waves of transient primitive progenitors and erythroid/myeloid progenitors (EMPs) unique to embryonic development arise from populations of hemogenic endothelium with distinct hematopoietic potential, as revealed by single cell–lineage tracking described in their study. Dll4 expression in some types of vascular stroma was shown to specifically promote myelopoiesis from the more multipotent EMPs identified in the study. The capacity to generate precursors to the definitive hematopoietic stem cell program (pre-HSC) remains to be determined, but use of appropriate stage-/organ-specific vascular stroma could play a role in differentially promoting this phase of hematopoiesis and subsequently supporting HSC expansion. Adapted from Figure 5I in the article by Rafii et al on page 770.