Lysophosphatidic acid acts as a nutrient‐derived developmental cue to regulate early hematopoiesis
Lysophosphatidic acid acts as a nutrient‐derived developmental cue to regulate early hematopoiesis
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DOI：
10.15252/embj.201387594
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发表时间：
2014-06
期刊：
影响因子：
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通讯作者：
Haisen Li;R. Yue;B. Wei;Ge Gao;Jiulin Du;G. Pei
中科院分区：
文献类型：
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作者：
Haisen Li;R. Yue;B. Wei;Ge Gao;Jiulin Du;G. Pei
原始造血发生在脊椎动物胚胎发生过程中的卵黄囊血岛，其中丰富的磷脂酰胆碱（PC）是发育胚胎的重要营养物质。然而，这些磷脂是否也产生促进造血的发育线索在很大程度上是未知的。在这里，我们表明，溶血磷脂酸（LPA），来自PC的信号分子，调节成血管细胞的形成和原始造血。LPA受体1（LPAR 1）或自身毒素（ATX）（一种催化LPA产生的分泌型溶血磷脂酶）的药理学和遗传学阻断抑制小鼠胚胎干细胞的造血分化，并损害成血管细胞的形成。机制实验表明ATX-LPA信号的调节作用是通过PI 3 K/Akt-Smad通路介导的。此外，在斑马鱼体内胚胎发生过程中，LPA作为成血管细胞形成和原始造血的发育线索。总之，我们确定LPA是原始造血的重要营养源性发育线索，也是成血管细胞调节的新机制。
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.