Mechanism of platelet production

血小板生成的分子机制仍不清楚。因此，我们研究了巨核细胞成熟过程的机制，血小板生成素(TPO)诱导的巨核细胞多倍化，成熟巨核细胞的前血小板形成，以及TPO诱导的分化信号转导。巨核细胞的多倍化是由于DNA复制而没有有丝分裂，但我们发现TPO诱导的骨髓原代巨核细胞通过异常的有丝分裂过程发生多倍化。巨核细胞进入有丝分裂，直到有丝分裂后期A，但在这个阶段，姐妹染色单体的距离不够远，不足以分离出细胞核。对于原血小板的形成，我们在体外发现了一种在血小板减少患者体内刺激小鼠原代巨核细胞的原血小板形成的因子。我们正试图通过各种层析技术来分离这一因子。我们还发现，NFE-2基因敲除小鼠的巨核细胞不能产生前血小板。因此，我们试图分离一种在NFE-2基因敲除小鼠中不表达的因子，并分离出一些有趣的因子。我们正在研究这些新因子的生物学功能。

Molecular mechanism of platelet production still remains unclear. Therefore, we investigated the mechanism of megakaryocyte maturation processes, thrombopoietin (Tpo)-induced polyploidization of megakaryocytes, proplatelet formation of matured megakaryocytes, and Tpo-induced differentiation signal transduction. It has been described that polyploidization of megakaryocytes is due to DNA replication without mitosis, but we found that Tpo-induced primary megakaryocytes from bone marrows undergo polyploidization through unusual mitotic process. Mekagaryocytes go into mitosis until anaphase A, but at this stage the sister chromatids Would not go far apart enough to be separated nuclei. As for proplatelet formation, we found a factor in thrombocytopenic patients which stimulates proplatelet formation of mouse primary megakaryocytes in vitro. We are trying to isolate this factor by various chromatographic techniques. We also found that proplatelets were not produced from the megakaryocytes of NFE-2 knock-out mice. Thus we attempted to isolate a factor which is not expressed in NFE-2 knock-out mice, and a number of interesting factors were isolated. We are investigating the biological functions of these new factors.