Megakaryocyte differentiation; cellular aspects and cytokine regulation

Classically, megakaryopoiesis is the differentiation process that results in platelet production from hematopoietic stem cells (HCS). This process compared to other hematopoietic cell differentiations is quite original by several aspects: (1) megakaryopoiesis can derive directly from the HSC, especially in case of stress, (2) megakaryopoiesis and erythropoiesis are two close cell lineages with a common progenitor, (3) megakaryocytes are mostly giant cells whose polyploidization is an integral part of the differentiation process and not dependent on a stress, (4) platelets originate from the fragmentation of the megakaryocyte cytoplasm with a production that depends both on the number and the size of megakaryocytes, (5) the process of fragmentation is active and depends on extrusion of long cytoplasmic extensions, called proplatelets into the vascular sinusoids of the bone marrow where they will break under the blood flow forces into preplatelets and then in platelets. These recent years have been marked by major advances in the understanding of these different aspects of megakaryopoiesis as well as on the role of thrombopoietin and its receptor called MPL in the regulation of platelet production. This knowledge has allowed a better understanding of many pathologies, in particular the mechanism of hereditary or acquired thrombocytopenia and thrombocytosis and has led to new therapies such as the clinical development of thrombopoietin receptor agonists. Recently, however, completely unexpected data have been obtained, questioning the function of megakaryocytes. Although the predominant function is the platelet production, megakaryocytes are heterogeneous, some of them are involved inside the hematopoietic niche in the regulation of the HSC quiescence and others in the immune response with functions close to those of monocytes or dendritic cells. Furthermore, the marrow is not the only site of megakaryopoiesis, but the lung is a second site with the development of an entire megakaryocyte differentiation, which may principally lead to immune megakaryocytes. In addition, megakaryocytes essentially of marrow origin located in the lung circulation are also present and involved in platelet production. These data open new perspectives on the role of megakaryocytes in the regulation of hematopoiesis and in the innate immunity, particularly during pulmonary infection.

Automated summary

Megakaryopoiesis is the process of platelet production from hematopoietic stem cells. It has several unique features compared to other hematopoietic cell differentiations. Recent advances have greatly improved our understanding of the different aspects of megakaryopoiesis and the regulation of platelet production. Furthermore, megakaryocytes can also be involved in hematopoietic regulation and immune response, and the lung is not only a site of platelet production but also a site of megakaryocyte differentiation.