Interplay of Pu.1 and gatal determines myelo-erythroid progenitor cell fate in zebrafish
Interplay of Pu.1 and gatal determines myelo-erythroid progenitor cell fate in zebrafish
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DOI：
10.1016/j.devcel.2004.11.014
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发表时间：
2005-01-01
影响因子：
11.8
通讯作者：
Kanki, JP
中科院分区：
文献类型：
--
作者：
Rhodes, J;Hagen, A;Kanki, JP
斑马鱼是研究胚胎脊椎动物造血的一个强有力的模型系统，允许进行细胞谱系确定的关键体内分析。在这项研究中，我们确定了斑马鱼骨髓红细胞祖细胞（MPC），可能代表的功能相当于哺乳动物共同的骨髓祖细胞。利用转基因pu.1-GFP鱼，实时MPC分化与细胞运动，形态和基因表达的动态变化相关。与哺乳动物的造血不同，胚胎斑马鱼的骨髓和红细胞生成发生在解剖学上分开的位置。基因敲除实验和移植试验证明了pu.1和gata 1的相互负调控及其非细胞自主调控，其决定了不同血液形成区域中髓系与红系MPC的命运。此外，在无血突变体cloche中强制表达pu.1导致了骨髓造血的拯救，这提供了有趣的证据，证明该基因可以在缺乏某些干细胞基因（如scl）的情况下发挥作用，控制骨髓造血。
The zebrafish is a powerful model system for investigating embryonic vertebrate hematopoiesis, allowing for the critical in vivo analysis of cell lineage determination. In this study, we identify zebrafish myeloerythroid progenitor cells (MPCs) that are likely to represent the functional equivalent of mammalian common myeloid progenitors. Utilizing transgenic pu.1-GFP fish, real-time MPC differentiation was correlated with dynamic changes in cell motility, morphology, and gene expression. Unlike mammalian hematopoiesis, embryonic zebrafish myelopoiesis and erythropoiesis occur in anatomically separate locations. Gene knockdown experiments and transplantation assays demonstrated the reciprocal negative regulation of pu.1 and gata1 and their non-cell-autonomous regulation that determines myeloid versus erythroid MPC fate in the distinct blood-forming regions. Furthermore, forced expression of pu.1 in the bloodless mutant cloche resulted in myelopoietic rescue, providing intriguing evidence that this gene can function in the absence of some stem cell genes, such as scl, in governing myelopoiesis.