Hematopoietic stem and progenitor cells maintain blood formation throughout our lifetime by undergoing long- and short-term self-renewal, respectively. As progenitor cells progress through the hematopoiesis process, their differentiation capabilities narrow, such that the precursors become committed to only one or two lineages. This Review focuses on recent advances in the identification and characterization of bipotent megakaryocytic-erythroid progenitors (MEP), the cells that can further produce two completely different functional outputs: platelets and red blood cells. The existence of MEP has sparked controversy as studies describing the requirement for this intermediate progenitor stage prior to commitment to the erythroid and megakaryocytic lineages have been potentially contradictory. Interpretation of these studies is complicated by the variety of species, cell sources, and analytical approaches used along with inherent challenges in the continuum of hematopoiesis, where hematopoietic progenitors do not stop at discrete steps on single paths as classically drawn in hematopoietic hierarchy models. With the goal of improving our understanding of human hematopoiesis, we discuss findings in both human and murine cells. Based on these data, MEP clearly represent a transitional stage of differentiation in at least one route to the generation of both megakaryocytes and erythroid cells. Stem Cells 2018;36:1138-1145.

© AlphaMed Press 2018.