Abstract
The mammalian yolk sac is known to play a prominent role in emergence of the hematopoietic system. The extent of this contribution has been a subject of debate in recent years largely due to effects of the early circulation that obscures the site of origin of hematopoietic stem and progenitor cells. This review discusses the limitations of some of the standard assays currently employed to study hematopoietic stem and progenitor cell emergence and highlights several recently reported novel methods that address this problem from new perspectives. Two methods directly alter the circulation by either preventing it from occurring in the first place or by removing vascular connections between the embryo and the yolk sac. Other approaches have altered the ability of hematopoietic cells to interact with their environment, resulting in the lack of migration or an inability to bind to potential hematopoietic niches. A third set of experiments utilize lineage tracing techniques to follow the migration of early progenitors once they enter the circulation. Taken together, these novel methods provide new evidence for the contribution of yolk sac hematopoietic stem and progenitor cells to the adult hematopoietic system.