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.