Erythro-myeloid progenitors can differentiate from endothelial cells and modulate embryonic vascular remodeling.
Erythro-myeloid progenitors can differentiate from endothelial cells and modulate embryonic vascular remodeling.
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DOI：
10.1038/srep43817
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发表时间：
2017-03-08
影响因子：
4.6
通讯作者：
Jones EA
中科院分区：
文献类型：
--
作者：
Kasaai B;Caolo V;Peacock HM;Lehoux S;Gomez-Perdiguero E;Luttun A;Jones EA
最近描述了红骨髓祖细胞（EMP）产生于卵黄囊内皮，就在血管重塑之前，并且是成人/出生后组织驻留巨噬细胞的来源。然而，关于EMP是否直接从内皮细胞分化还是仅仅通过内皮细胞的问题仍然存在。我们提供的第一个证据表明，在体内的电磁脉冲可以出现直接从内皮细胞（EC），并证明这些细胞在血管发育中的作用。我们发现，EMPs表达大多数EC标志物，但晚期EMPs和EMP-derived细胞不像EC那样摄取乙酰化低密度脂蛋白（AcLDL）。当在EMP分化之前用AcLDL标记内皮时，就会产生AcLDL+的EMP和EMP衍生细胞。然而，如果在EMP分化开始后注射AcLDL，大多数EMP衍生的细胞不会被双标记。我们发现，细胞分裂之前进入循环的电磁脉冲，和血流促进过渡的电磁脉冲从内皮细胞进入循环中的一氧化氮依赖的方式。在功能获得性研究中，我们在胚胎中注射CSF 1-Fc配体，发现这增加了CSF 1 R+细胞的数量，这些细胞定位于静脉丛并显著破坏静脉重塑。这是第一项明确确定EMPs来自体内内皮细胞的研究，并显示了早期髓样细胞在血管发育中的作用。
Erythro-myeloid progenitors (EMPs) were recently described to arise from the yolk sac endothelium, just prior to vascular remodeling, and are the source of adult/post-natal tissue resident macrophages. Questions remain, however, concerning whether EMPs differentiate directly from the endothelium or merely pass through. We provide the first evidence in vivo that EMPs can emerge directly from endothelial cells (ECs) and demonstrate a role for these cells in vascular development. We find that EMPs express most EC markers but late EMPs and EMP-derived cells do not take up acetylated low-density lipoprotein (AcLDL), as ECs do. When the endothelium is labelled with AcLDL before EMPs differentiate, EMPs and EMP-derived cells arise that are AcLDL+. If AcLDL is injected after the onset of EMP differentiation, however, the majority of EMP-derived cells are not double labelled. We find that cell division precedes entry of EMPs into circulation, and that blood flow facilitates the transition of EMPs from the endothelium into circulation in a nitric oxide-dependent manner. In gain-of-function studies, we inject the CSF1-Fc ligand in embryos and found that this increases the number of CSF1R+ cells, which localize to the venous plexus and significantly disrupt venous remodeling. This is the first study to definitively establish that EMPs arise from the endothelium in vivo and show a role for early myeloid cells in vascular development.