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首页> 外文期刊>EMBO Journal >Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis
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Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis

机译：Lysophosphatidic酸作为nutrient-derived发展线索来调节早期造血作用

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摘要

Primitive hematopoiesis occurs in the yolk sac blood islands during vertebrate embryogenesis, where abundant phosphatidylcholines (PC) are available as important nutrients for the developing embryo. However, whether these phospholipids also generate developmental cues to promote hematopoiesis is largely unknown. Here, we show that lysophosphatidic acid (LPA), a signaling molecule derived from PC, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 (LPAR1) or autotoxin (ATX), a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. Mechanistic experiments revealed that the regulatory effect of ATX-LPA signaling was mediated by PI3K/Akt-Smad pathway. Furthermore, during in vivo embryogenesis in zebrafish, LPA functioned as a developmental cue for hemangioblast formation and primitive hematopoiesis. Taken together, we identified LPA as an important nutrient-derived developmental cue for primitive hematopoiesis as well as a novel mechanism of hemangioblast regulation. Synopsis Yolk sac phosphatidylcholines serve not only nutrient roles for the developing embryo, but can also give rise to signaling molecules that are here shown to regulate hemangioblast formation and primitive hematopoiesis in vertebrates. Pharmocological and genetic blockage of LPA signaling impairs hemangioblast formation and hematopoietic differentiation of mouse embryonic stem cells (mESCs). LPA signaling regulates mESCs hematopoietic differentiation through activating PI3K/Akt-Smad pathway. LPA signaling is required for hemangioblast formation and primitive hematopoiesis in zebrafish. Yolk sac phosphatidylcholines serve not only nutrient roles for the developing embryo, but can also give rise to signaling molecules that are here shown to regulate hemangioblast formation and primitive hematopoiesis in vertebrates.
机译：原始造血作用发生在卵黄囊血岛在脊椎动物胚胎发生过程中,在丰富的磷脂酰胆碱(PC)吗作为重要的营养物质胚胎发育过程中。磷脂还生成发展的线索促进造血作用在很大程度上是未知的。我们表明,lysophosphatidic酸(LPA)信号分子来自PC,监管hemangioblast形成和原始造血作用。堵塞LPA受体1 (LPAR1)或自体毒素(ATX)分泌溶血磷脂酶催化LPA生产、抑制造血小鼠胚胎干细胞的分化受损hemangioblasts的形成。机械的实验显示监管ATX-LPA信号的影响由PI3K / Akt-Smad途径。在斑马鱼体内胚胎发生期间,LPA充当一个发展线索hemangioblast形成和原始造血作用。作为一种重要的nutrient-derived发育对原始造血作用以及线索小说hemangioblast监管机制。剧情简介卵黄囊磷脂酰胆碱不服务只有发展胚胎营养作用,但也可以产生信号分子在这里显示调节hemangioblast形成与原始造血作用脊椎动物。LPA信号削弱hemangioblast形成和小鼠造血分化胚胎干细胞(制)。监管公司的造血分化通过激活PI3K / Akt-Smad途径。信号需要hemangioblast形成在斑马鱼和原始造血作用。囊磷脂酰胆碱不仅营养服务角色的胚胎发育过程中,但也可以产生信号分子hemangioblast形成和调节原始脊椎动物的造血作用。

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