Erythro-myeloid progenitors contribute endothelial cells to developing blood vessels

The earliest blood vessels in the mammalian embryo are formed when endothelial cells (ECs) differentiate from angioblasts and coalesce into tubular networks. Thereafter, the en-dothelium is thought to expand solely by proliferation of pre-existing ECs. Here we show that the earliest precursors of erythrocytes, megakaryocytes and macrophages, the yolk sac-derived erythro-myeloid progenitors (EMPs), provide a complementary source of ECs that are recruited into pre-existing vasculature. Whereas a first wave of yolk sac-resident EMPs contributes ECs to the yolk sac endothelium, a second wave of EMPs colonises the embryo and contributes ECs to intraembryonic endothelium in multiple organs, where they persist into adulthood. By demonstrating that EMPs constitute a hitherto unrecognised source of ECs, we reveal that embryonic blood vascular endothelium expands in a dual mechanism that involves both the proliferation of pre-existing ECs and the incorporation of ECs derived from hematopoietic precursors. RNAseq analysis of FACS-isolated tdTom+ and tdTom- ECs from E12.5 Csf1r-iCre;RosatdTom embryos.哺乳动物胚胎中最早的血管，由成血管细胞分化为内皮细胞（endothelial cells，ECs）并聚合形成管状网络而生成。此后，学界普遍认为内皮组织仅通过已存在的ECs的增殖实现扩张。本研究表明，红细胞、巨核细胞与巨噬细胞的最早前体——卵黄囊来源的红髓系祖细胞（erythro-myeloid progenitors，EMPs），可提供另一类ECs来源，这类细胞会被招募至已存在的脉管系统中。驻留于卵黄囊的第一波EMPs可为卵黄囊内皮提供ECs，而第二波EMPs则定植于胚胎内部，并为多个器官的胚胎内内皮提供ECs，这些细胞可存活至成年阶段。本研究证实EMPs是一类迄今未被发现的ECs来源，由此揭示胚胎血管内皮的扩张存在双重机制：既依赖已存在ECs的增殖，也包含源自造血前体细胞的ECs的整合。本研究对发育第12.5天（E12.5）的Csf1r-iCre;RosatdTom胚胎中，经荧光激活细胞分选（FACS）分离的tdTom阳性与tdTom阴性ECs开展了RNA测序（RNAseq）分析。