From hematopoietic stem cells to platelets
From hematopoietic stem cells to platelets
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DOI：
10.1111/j.1538-7836.2007.02472.x
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发表时间：
2007-07-01
影响因子：
10.4
通讯作者：
Vainchenker, W.
中科院分区：
文献类型：
--
作者：
Chang, Y.;Bluteau, D.;Vainchenker, W.
巨核细胞生成是导致血小板产生的过程。这一过程包括多能造血干细胞向巨核细胞（MK）祖细胞的转化、巨核细胞祖细胞的增殖和分化、巨核细胞前体的多倍体化和巨核细胞的成熟。成熟的巨核细胞通过一个动态和受调节的过程产生血小板，称为前血小板形成，由在血流中断裂的长伪足延长组成。最近的研究表明，MK和红系谱系在细胞和分子水平上密切相关，特别是在调节其分化程序的转录因子方面。巨核细胞生成受两类转录因子调控，一类是调节分化过程的转录因子，如GATA-1，另一类是调节血小板形成的转录因子，如NF-E2。体液因子血小板生成素（TPO）是通过刺激其受体MPL来调节MK分化和血小板生成的主要因子。许多MK谱系的获得性或先天性病理现在可以通过巨核细胞生成、Tpo或c-mpl基因以及与MPL相关的信号分子中转录因子活性的分子异常来解释。最近发展的MPL激动剂可能为治疗某些血小板减少症提供有效的药物。
Megakaryocytopoiesis is the process that leads to the production of platelets. This process involves the commitment of multipotent hematopoietic stem cells toward megakaryocyte (MK) progenitors, the proliferation and differentiation of MK progenitors, the polyploidization of MK precursors and the maturation of MK. Mature MK produce platelets by cytoplasmic fragmentation occurring through a dynamic and regulated process, called proplatelet formation, and consisting of long pseudopodial elongations that break in the blood flow. Recent insights have demonstrated that the MK and erythroid lineages are tightly associated at both the cellular and molecular levels, especially in the transcription factors that regulate their differentiation programs. Megakaryocytopoiesis is regulated by two types of transcription factors, those regulating the differentiation process, such as GATA-1, and those regulating proplatelet formation, such as NF-E2. The humoral factor thrombopoietin (TPO) is the primary regulator of MK differentiation and platelet production through the stimulation of its receptor MPL. Numerous acquired or congenital pathologies of the MK lineage are now explained by molecular abnormalities in the activity of the transcription factors involved in megakaryocytopoiesis, in the Tpo or c-mpl genes, as well as in signaling molecules associated with MPL. The recent development of MPL agonists may provide efficient agents for the treatment of some thrombocytopenias.