Loss of Gata1 but not Gata2 converts erythropoiesis to myelopoiesis in zebrafish embryos
Loss of Gata1 but not Gata2 converts erythropoiesis to myelopoiesis in zebrafish embryos
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DOI：
10.1016/j.devcel.2004.12.001
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发表时间：
2005-01-01
影响因子：
11.8
通讯作者：
Zon, LI
中科院分区：
文献类型：
--
作者：
Galloway, JL;Wingert, RA;Zon, LI
造血祖细胞分化为红系或髓系细胞系被认为取决于转录因子gata 1和pu.1的相对水平。虽然功能丧失分析表明，gata 1是必要的终末红细胞分化，没有研究表明，gata 1的损失改变个体发育过程中的髓系分化。在这里，我们提供了体内证据表明，Gata 1而不是Gata 2的丢失将原始血液前体转化为骨髓细胞，导致粒细胞中性粒细胞和巨噬细胞以红细胞为代价大量扩增。除了这种命运的变化，许多红细胞基因的表达被发现是差异依赖于Gata 1单独，Gata 1和Gata 2，或独立的加塔因素，表明多种途径调节红细胞基因的表达。我们的研究建立了造血过程中加塔因子依赖的转录层次结构，并证明了gata 1在胚胎发生过程中指导骨髓-红细胞系命运决定中起着不可或缺的作用。
The differentiation of hematopoietic progenitors into erythroid or myeloid cell lineages is thought to depend upon relative levels of the transcription factors gata1 and pu.1. While loss-of-function analysis shows that gata1 is necessary for terminal erythroid differentiation, no study has demonstrated that loss of gata1 alters myeloid differentiation during ontogeny. Here we provide in vivo evidence that loss of Gata1, but not Gata2, transforms primitive blood precursors into myeloid cells, resulting in a massive expansion of granulocytic neutrophils and macrophages at the expense of red blood cells. In addition to this fate change, expression of many erythroid genes was found to be differentially dependent on Gata1 alone, on both Gata1 and Gata2, or independent of both Gata factors, suggesting that multiple pathways regulate erythroid gene expression. Our studies establish a transcriptional hierarchy of Gata factor dependence during hematopoiesis and demonstrate that gata1 plays an integral role in directing myelo-erythroid lineage fate decisions during embryogenesis.