Sumanas Saulius, Gomez Gustavo, Zhao Yan, Park Changwon, Choi Kyunghee, Lin Shuo
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, USA.
Blood. 2008 May 1;111(9):4500-10. doi: 10.1182/blood-2007-09-110569. Epub 2008 Feb 12.
Vascular endothelial and myeloid cells have been proposed to originate from a common precursor cell, the hemangioblast. The mechanism of endothelial and myeloid cell specification and differentiation is poorly understood. We have previously described the endothelial-specific zebrafish Ets1-related protein (Etsrp), which was both necessary and sufficient to initiate vasculogenesis in the zebrafish embryos. Here we identify human Etv2/ER71 and mouse ER71 proteins as functional orthologs of Etsrp. Overexpression of mouse ER71 and Etsrp caused strong expansion of hemangioblast and vascular endothelial lineages in a zebrafish embryo. In addition, we show that etsrp is also required for the formation of myeloid but not erythroid cells. In the absence of etsrp function, the number of granulocytes and macrophages is greatly reduced. Etsrp overexpression causes expansion of both myeloid and vascular endothelial lineages. Analysis of mosaic embryos indicates that etsrp functions cell autonomously in inducing myeloid lineage. We further demonstrate that the choice of endothelial versus myeloid fate depends on a combinatorial effect of etsrp, scl, and alk8 genes.
血管内皮细胞和髓系细胞被认为起源于一种共同的前体细胞——成血管细胞。内皮细胞和髓系细胞的特化及分化机制尚不清楚。我们之前描述过内皮细胞特异性的斑马鱼Ets1相关蛋白（Etsrp），它对于启动斑马鱼胚胎中的血管生成既必要又充分。在此，我们鉴定出人类Etv2/ER71蛋白和小鼠ER71蛋白是Etsrp的功能直系同源物。小鼠ER71和Etsrp的过表达导致斑马鱼胚胎中成血管细胞和血管内皮谱系的强烈扩展。此外，我们表明Etsrp对于髓系细胞而非红系细胞的形成也是必需的。在缺乏Etsrp功能时，粒细胞和巨噬细胞的数量会大幅减少。Etsrp的过表达导致髓系和血管内皮谱系都扩展。对嵌合胚胎的分析表明，Etsrp在诱导髓系谱系中以细胞自主方式发挥作用。我们进一步证明，内皮细胞与髓系细胞命运的选择取决于Etsrp、scl和alk8基因的组合效应。
