The Road Map for Megakaryopoietic Lineage from Hematopoietic Stem/Progenitor Cells

Megakaryocytes (Mgks) are terminally differentiated blood cells specified to produce platelets, whereas hematopoietic stem cells (HSCs) are the most undifferentiated blood cells that retain multipotency to produce all kinds of blood cells. As such, these two cell types reside at the bottom and the top of the hematopoietic hierarchy, respectively. In spite of this distance, they share several important cell surface molecules as well as transcription factors. In the conventional step-wise differentiation model, HSCs gradually lose their self-renewal capacity and differentiate into multipotent progenitors (MPPs), which is the first branch point of myeloid and lymphoid lineage. In this model, common myeloid progenitors can differentiate into bipotent Mgk/erythroid progenitors (MEPs), and MEPs eventually differentiate into unipotent mature Mgks. However, it has been recently reported that a subpopulation within the HSC and MPP compartments demonstrates an Mgk-biased differentiation potential. These reports imply that revisions to the HSC-to-Mgk differentiation pathway should be discussed. In this review, we summarize recent findings about Mgk differentiation from HSCs and discuss future directions in this research field. Stem Cells Translational Medicine 2017;6:1661-1665.