The transcription factor ZBP-89 controls generation of the hematopoietic lineage in zebrafish and mouse embryonic stem cells
The transcription factor ZBP-89 controls generation of the hematopoietic lineage in zebrafish and mouse embryonic stem cells
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DOI：
10.1242/dev.02540
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发表时间：
2006-09-15
期刊：
影响因子：
4.6
通讯作者：
Arnaout, M. Amin
中科院分区：
文献类型：
--
作者：
Li, Xiangen;Xiong, Jing-Wei;Arnaout, M. Amin
造血发育与血管发育密切相关，这两个过程在很大程度上受控制细胞命运决定和细胞分化的转录因子的调节。血液和血管都源自一个共同的祖细胞，称为成血管细胞，但指定该干细胞群体发育和分化为造血和血管谱系的因素仍然不清楚。在这里，我们报告说，敲低Kruppel样转录因子ZBP-89在斑马鱼胚胎中的结果，在一个无血表型，造成破坏的原始和永久的造血，而保持初级血管形成完整。注射ZBP-89 mRNA到缺乏造血和内皮细胞谱系的钟形斑马鱼胚胎中，拯救了造血，但没有血管发生。注射干细胞白血病（SCL）的mRNA，一种指导成血管细胞发育成血细胞前体的转录因子，拯救了ZBP-89斑马鱼变形体中的无血表型。ZBP-89的强制表达诱导野生型斑马鱼和小鼠胚胎干细胞培养物中造血祖细胞的扩增，但抑制体内和体外血管生成。这些发现确立了ZBP-89的独特调节作用，其定位于早期血液和血管发育之间的界面。
Hematopoietic development is closely linked to that of blood vessels and the two processes are regulated in large part by transcription factors that control cell fate decisions and cellular differentiation. Both blood and blood vessels derive from a common progenitor, termed the hemangioblast, but the factor(s) specifying the development and differentiation of this stem cell population into the hematopoietic and vascular lineages remain ill defined. Here, we report that knockdown of the Kruppel- like transcription factor ZBP-89 in zebrafish embryos results in a bloodless phenotype, caused by disruption of both primitive and definitive hematopoiesis, while leaving primary blood vessel formation intact. Injection of ZBP-89 mRNA into cloche zebrafish embryos, which lack both the hematopoietic and endothelial lineages, rescues hematopoiesis but not vasculogenesis. Injection of mRNA for Stem Cell Leukemia (SCL), a transcription factor that directs hemangioblast development into blood cell precursors, rescues the bloodless phenotype in ZBP-89 zebrafish morphants. Forced expression of ZBP-89 induces the expansion of hematopoietic progenitors in wildtype zebrafish and in mouse embryonic stem cell cultures but inhibits angiogenesis in vivo and in vitro. These findings establish a unique regulatory role for ZBP-89, positioned at the interface between early blood and blood vessel development.