Bipotent megakaryocytic-erythroid progenitors: Concepts and controversies

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, and at the point where potential limits the fate, and 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 cell that can further produce two completely different functional outputs: platelets and red blood cells. Potentially contradicting data have been published on the presence of MEP. Additionally, studies describing the requirement for this intermediate progenitor stage prior to commitment to the erythroid and megakaryocytic lineages can be contradictory. Interpretation of these studies is complicated by the variety of species, cell sources, and analytical approaches used along with the inherent challenge 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 represents a transitional stage of differentiation in at least one route to the generation of both megakaryocytes and erythroid cells.