Abstract
Megakaryocytes (Mks) are rare polyploid bone marrow cells whose function is to produce blood platelets. Since the purification and cloning of the major Mk cytokine, thrombopoietin, in 1994, considerable progress has been made in understanding the biology of Mk development. Remarkably, these advances have revealed a number of key features of Mks that are shared with hematopoietic stem cells (HSCs), such as common surface receptors, lineage-specific transcription factors, and specialized signaling pathways. Why there should be such a close connection between these two cell types remains unclear. In this Prospect article, we summarize the data supporting these shared features and speculate on possible teleological bases. In particular, we focus on common links involving developmental hierarchy, endothelial cells, and bone marrow niche interactions. This discussion highlights new data showing close ontologic relationship between HSCs and specialized "hemogenic" endothelial cells during development, and functional overlap between Mks/platelets and endothelial cells. Overall, these findings may be of relevance in the development of techniques for HSC ex vivo culture and/or possible generation of HSCs via somatic cell reprogramming.