New insights into the generation and function of megakaryocytes in health and disease

Megakaryocytes are canonically viewed as specialized hematopoietic cells that merely produce platelets and that are generated through a series of hematopoietic stem and progenitor cells in the bone marrow. Despite their essential physiological functions, the generation and function of megakaryocytes remain incompletely understood. Recent studies, mostly in mice, have begun to redefine the cellular hierarchy of megakaryopoiesis, and shed new light on the alternative routes and mechanisms of megakaryopoiesis. Moreover, the conception of megakaryocytes as a homogeneous cell population with the sole purpose of platelet production is being challenged. Indeed, megakaryocytes are being shown to be a heterogeneous population of cells with distinct routes of differentiation and versatile functions. In particular, megakaryocytes show abilities reminiscent of immune cells, and are increasingly considered as the root dictating the hemostatic and immune functions of platelets in various physiopathological conditions. Furthermore, although megakaryocytes are well known as a component of the bone marrow niche, maintaining hematopoietic stem cells during homeostasis, the newly identified properties of megakaryocytes further indicate that they may be key supporters of stressed or diseased hematopoietic stem cells during myeloablative injury, aging and hematopoietic malignancy. Therefore, the generation and function of megakaryocytes are more diverse than we previously thought. Here, we review the recent literature that expands our views of megakaryocyte differentiation and heterogeneity, as well as the functions of megakaryocytes, with special focuses on their immune functions and supporting roles for stressed or diseased hematopoietic stem cells.