Thrombopoietin Induces Megakaryocyte Differentiation in Hematopoietic Progenitor FDC-P2 Cells (*)
Thrombopoietin Induces Megakaryocyte Differentiation in Hematopoietic Progenitor FDC-P2 Cells (*)
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血小板生成素诱导造血祖细胞 FDC-P2 巨核细胞分化 (*)
DOI：
10.1074/jbc.270.34.19673
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
K. Todokoro
中科院分区：
文献类型：
--
作者：
Y. Nagata;H. Nagahisa;Y. Aida;K. Okutomi;T. Nagasawa;K. Todokoro
血小板生成素（Tpo）是一种特异性调节巨核细胞成熟和血小板生成的细胞因子。目前对TPO诱导巨核细胞成熟的分子和细胞机制知之甚少，包括多倍体化和血小板释放。为了研究Tpo诱导的巨核细胞分化，从白细胞介素-3依赖性造血祖细胞系FDC-P2建立了小鼠细胞系FD-TPO，其响应Tpo并与Tpo一起生长。表达内源性Tpo受体的FD-TPO细胞与Tpo呈剂量依赖性生长。此外，Tpo刺激显著诱导FD-TPO细胞中巨核细胞/红系特异性转录因子加塔-1和NF-E2的表达。流式细胞术分析表明，血小板特异性细胞表面抗原，包括CD 61（GPIIIa）的表达显着增加TPO刺激的FD-TPO细胞和骨髓特异性抗原，Gr-1和Mac-1的表达，减少。因此，我们得出结论，Tpo的结合FD-TPO细胞不仅诱导细胞生长，但也分化成成熟的巨核细胞样细胞，因此该细胞系被发现是有用的Tpo受体介导的生长和分化信号的研究。
Thrombopoietin (Tpo) is a cytokine that specifically regulates megakaryocyte maturation and platelet production. Little is known about the molecular and cellular mechanism of the Tpo-induced megakaryocyte maturation process including polyploidization and platelet release. To study Tpo-induced megakaryocyte differentiation, a mouse cell line FD-TPO, which responds and grows with Tpo, was established from a interleukin-3-dependent hematopoietic progenitor cell line FDC-P2. The FD-TPO cells, expressing endogenous Tpo receptor, grew with Tpo in a dose-dependent manner. Further, Tpo stimulation dramatically induced expression of megakaryocyte/erythroid-specific transcription factors GATA-1 and NF-E2 in FD-TPO cells. Flow cytometry analysis demonstrated that expression of platelet-specific cell surface antigens including CD61 (GPIIIa) dramatically increased in Tpo-stimulated FD-TPO cells and that expression of myeloid-specific antigens, Gr-1 and Mac-1, decreased. Therefore, we concluded that the binding of Tpo to FD-TPO cells induces not only cell growth but also differentiation into mature megakaryocyte-like cells, and thus this cell line was found to be useful for the study of Tpo receptor-mediated growth and differentiation signals.