UCL Institute of Ophthalmology, University College London, London, UK.
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
Nature. 2018 Oct;562(7726):223-228. doi: 10.1038/s41586-018-0552-x. Epub 2018 Sep 26.
The earliest blood vessels in mammalian embryos are formed when endothelial cells differentiate from angioblasts and coalesce into tubular networks. Thereafter, the endothelium is thought to expand solely by proliferation of pre-existing endothelial cells. Here we show that a complementary source of endothelial cells is recruited into pre-existing vasculature after differentiation from the earliest precursors of erythrocytes, megakaryocytes and macrophages, the erythro-myeloid progenitors (EMPs) that are born in the yolk sac. A first wave of EMPs contributes endothelial cells to the yolk sac endothelium, and a second wave of EMPs colonizes the embryo and contributes endothelial cells to intraembryonic endothelium in multiple organs, where they persist into adulthood. By demonstrating that EMPs constitute a hitherto unrecognized source of endothelial cells, we reveal that embryonic blood vascular endothelium expands in a dual mechanism that involves both the proliferation of pre-existing endothelial cells and the incorporation of endothelial cells derived from haematopoietic precursors.
哺乳动物胚胎中的最早血管是由内皮细胞从成血管细胞分化并融合成管状网络形成的。此后，人们认为内皮细胞仅通过已有内皮细胞的增殖来扩张。在这里，我们表明，在分化为最早的红细胞、巨核细胞和巨噬细胞前体（在蛋黄囊中产生的红髓祖细胞，erythro-myeloid progenitors，EMPs）之后，内皮细胞的另一个补充来源会被招募到已有脉管系统中。第一波 EMP 为蛋黄囊内皮提供内皮细胞，第二波 EMP 定植于胚胎中，并为多个器官的胚胎内内皮提供内皮细胞，这些细胞在成年期仍然存在。通过证明 EMP 构成了一个以前未被识别的内皮细胞来源，我们揭示了胚胎血管内皮通过涉及已有内皮细胞增殖和来自造血前体的内皮细胞整合的双重机制来扩张。
