Studies of Murine Megakaryocyte Colony Size and Ploidization

Abstract

Megakaryocytes are the product of a series of proliferative and differentiative steps involving a complex cellular hierarchy. Pluripotent stem cells undergo a progressive narrowing in their differentiative potential eventually giving rise to unipotent progenitor cells committed to the megakaryocytic lineage. These cells, which are operationally termed colony-forming units — megakaryocyte (CFU-Meg), undergo varying numbers of mitotic divisions, giving rise to a class of cells often referred to as promegakaryoblasts. These diploid cells cease cell division but, instead, undergo a series of synchronous nuclear endoreduplications or endomitoses, giving rise to the unique polyploid cells megakaryocytes. Megakaryocyte colony formation represents an in vitro model of these processes in which colony size reflects the mitotic activity of megakaryocytic progenitor cells while the ploidy of colony cells is determined by the endomitotic activity of promegakaryoblasts and their descendants. Therefore, it might be expected that the analysis of megakaryocytic colony size and the ploidy of colony cells could provide insight into the cellular responses which underlie megakaryocytopoietic regulation in vivo.