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

Abstract

Megakaryocytes (MKs) are canonically viewed as specialized hematopoietic cells merely producing platelets and generated through a series of hematopoietic stem and progenitor cells in the bone marrow (BM). Despite essential physiological functions, the generation and function of MKs remain incompletely understood. Recent studies, almost 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 MKs as a homogenous cell population with the sole purpose of platelet production is being challenged. Conversely, MKs are shown to be a heterogenous cell population with distinct differentiation routes and versatile functions. Especially, MKs 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 been well known as a component of the BM niche maintaining hematopoietic stem cells (HSCs) during homeostasis, the newly-identified properties of MKs further make them a key supporter for stressed or diseased HSCs during myeloablative injury, aging and hematopoietic malignancy. Therefore, the generation and function of MKs are more diverse than we previously thought. Here, we review the recent literatures that expand our views of MK differentiation and heterogeneity, as well as of MK functions with special focuses on their immune functions and supporting roles for stressed or diseased HSCs.