From the Division of Hematology, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA.
Arterioscler Thromb Vasc Biol. 2019 Jul;39(7):1288-1300. doi: 10.1161/ATVBAHA.119.312129. Epub 2019 May 2.
Megakaryocytes are hematopoietic cells, which are responsible for the production of blood platelets. The traditional view of megakaryopoiesis describes the cellular journey from hematopoietic stem cells, through a hierarchical series of progenitor cells, ultimately to a mature megakaryocyte. Once mature, the megakaryocyte then undergoes a terminal maturation process involving multiple rounds of endomitosis and cytoplasmic restructuring to allow platelet formation. However, recent studies have begun to redefine this hierarchy and shed new light on alternative routes by which hematopoietic stem cells are differentiated into megakaryocytes. In particular, the origin of megakaryocytes, including the existence and hierarchy of megakaryocyte progenitors, has been redefined, as new studies are suggesting that hematopoietic stem cells originate as megakaryocyte-primed and can bypass traditional lineage checkpoints. Overall, it is becoming evident that megakaryopoiesis does not only occur as a stepwise process, but is dynamic and adaptive to biological needs. In this review, we will reexamine the canonical dogmas of megakaryopoiesis and provide an updated framework for interpreting the roles of traditional pathways in the context of new megakaryocyte biology. Visual Overview- An online visual overview is available for this article.
巨核细胞是造血细胞,负责生成血小板。传统的巨核细胞生成观点描述了从造血干细胞开始的细胞旅程,通过一系列层次分明的祖细胞,最终生成成熟的巨核细胞。一旦成熟,巨核细胞随后经历一个涉及多次核内有丝分裂和细胞质重构的终末成熟过程,以允许血小板形成。然而,最近的研究开始重新定义这个层次结构,并揭示了造血干细胞分化为巨核细胞的替代途径。特别是,巨核细胞的起源,包括巨核细胞祖细胞的存在和层次结构,已经被重新定义,因为新的研究表明造血干细胞起源于巨核细胞前体细胞,可以绕过传统的谱系检查点。总的来说,越来越明显的是,巨核细胞生成不仅作为一个逐步的过程发生,而且是动态的,并适应于生物学需求。在这篇综述中,我们将重新审视巨核细胞生成的经典教条,并提供一个更新的框架来解释传统途径在新的巨核细胞生物学背景下的作用。在线概览-本文提供了一个在线概览。