Ddx46 Is Required for Multi-Lineage Differentiation of Hematopoietic Stem Cells in Zebrafish
Ddx46 Is Required for Multi-Lineage Differentiation of Hematopoietic Stem Cells in Zebrafish
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DOI：
10.1089/scd.2012.0623
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发表时间：
2013-09-15
影响因子：
4
通讯作者：
Kikuchi, Yutaka
中科院分区：
文献类型：
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作者：
Hirabayashi, Ryo;Hozumi, Shunya;Kikuchi, Yutaka
平衡和精确控制造血干细胞（hsc）向所有血液谱系的自我更新和分化过程对脊椎动物的最终造血至关重要。然而，造血干细胞维持和分化的分子机制尚未完全阐明。在这里，我们发现斑马鱼编码DEAD-box RNA解旋酶的Ddx46在尾侧造血组织（CHT）的造血干细胞中表达。在Ddx46突变体中，表达cmyb或t细胞急性淋巴细胞白血病1 （tal1）分子标记的造血干细胞数量明显减少。然而，在受精后48小时，突变体的CHT中没有检测到hsc的大量细胞死亡，并且hsc的增殖正常。我们发现，在Ddx46突变体中，骨髓生成发生，但红细胞生成和淋巴生成被抑制。与这些结果一致的是，编码髓细胞发育调节剂的spi1的表达得以维持，而编码红细胞发育调节剂的gata1a的表达在突变体中被下调。综上所述，我们的研究结果首次提供了遗传证据，证明斑马鱼通过调节特定基因的表达，在造血干细胞发育过程中实现多系分化。
Balanced and precisely controlled processes between self-renewal and differentiation of hematopoietic stem cells (HSCs) into all blood lineages are critical for vertebrate definitive hematopoiesis. However, the molecular mechanisms underlying the maintenance and differentiation of HSCs have not been fully elucidated. Here, we show that zebrafish Ddx46, encoding a DEAD-box RNA helicase, is expressed in HSCs of the caudal hematopoietic tissue (CHT). The number of HSCs expressing the molecular markers cmyb or T-cell acute lymphocytic leukemia 1 (tal1) was markedly reduced in Ddx46 mutants. However, massive cell death of HSCs was not detected, and proliferation of HSCs was normal in the CHT of the mutants at 48h postfertilization. We found that myelopoiesis occurred, but erythropoiesis and lymphopoiesis were suppressed, in Ddx46 mutants. Consistent with these results, the expression of spi1, encoding a regulator of myeloid development, was maintained, but the expression of gata1a, encoding a regulator of erythrocyte development, was downregulated in the mutants. Taken together, our results provide the first genetic evidence that zebrafish Ddx46 is required for the multilineage differentiation of HSCs during development, through the regulation of specific gene expressions.