The Unfinished Story of Megakaryopoiesis

Since their nineteenth-century discovery, megakaryocytes (MKs) and the platelets they produce have remained among the least understood lineages in hematology. Understanding megakaryopoiesis and thrombopoiesis is essential for deciphering hematological disorders and developing platelet biomanufacturing and cell-based therapies. We revisit MK and platelet biogenesis, from MK emergence from hematopoietic stem cells to platelet release through proplatelet formation and cytoplasmic fragmentation. The growing complexity of differentiation pathways challenges the classical hierarchical view of hematopoiesis. Many concepts established in mice remain insufficiently validated in humans, motivating 3D bioengineered models for disease study that may rewrite key chapters in human platelet biology.