Erythro-myeloid progenitors contribute endothelial cells to blood vessels

Abstract

The earliest blood vessels in the mammalian embryo are formed when endothelial cells (ECs) differentiate from angioblasts and coalesce into tubular networks. Thereafter, the endothelium 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.

Dermomyotome-derived endothelial cells migrate to the dorsal aorta to support hematopoietic stem cell emergence

“…Future work should help determine if distinct regions within the mesoderm can give rise to functionally divergent subsets of angioblasts. Plasticity of EC development is further illustrated from recent work that surprisingly showed that extraembryonic derived erythomyeloid progenitors can give rise to up to 60% of liver ECs in mice (Plein et al, 2018). progenitors.…”

“…Lateral plate mesoderm (LPM) is known to be the primary source of ECs across vertebrate phyla (Potente and Makinen, 2017). However, recent findings have suggested that ECs can arise from distinct mesodermal derivatives, including extraembryonicderived erythromyeloid progenitors (EMPs), that contribute extensively to the murine kidney vasculature (Plein et al, 2018). Similarly, there is evidence in rodents and other amniotes, that paraxial mesoderm (PM) also generates a contingent of ECs that contribute to the embryonic vasculature (Ambler et al, 2001;Esner et al, 2006;Noden, 1989;Pardanaud et al, 1996;Pouget et al, 2006;Pouget et al, 2008;Wilting et al, 1995;Yvernogeau et al, 2012).…”

Monocytes as Endothelial Progenitor Cells (EPCs), Another Brick in the Wall to Disentangle Tumor Angiogenesis

“…Some reports addressing EPCs and disease, such as systemic sclerosis, showed contradictory and discrepant results about EPCs mobilization and differentiation; in part, because there is a lack of a precise panel of cell surface markers used for the characterization of this subset of cells [4][5][6][7][8][9][10]. In mouse embryonic vascular endothelium, erythro-myeloid progenitors (EMPs) can differentiate into ECs [11] and in a mouse model of carotid injury, monocytes (CD14 + cells) are capable of improving re-endothelialization [12]. In vivo and in vitro targeting of Tie2-monocytes decreases angiogenesis by abrogating EC proliferation [13][14][15] and an in vivo CCR2 (chemokine (C-C motif) receptor 2) knockout impairs monocytes recruitment and VEGFA (also named VEGF, vascular endothelial growth factor) expression, accompanied by a reduction in the angiogenesis rate [16].…”

Haematopoietic stem cell reprogramming and the hope for a universal blood product

“…1, yellow labels). In Plein et al, the vasculature of the embryo is shown to develop from two distinct lineages: in addition to mesoderm-derived ECs, the authors observed that a complementary source of endothelium is recruited into the pre-existing vasculature through transdifferentiation of erythro-myeloid progenitors (EMPs) that emerge in the yolk sac [32]. Although this updated strategy yielded cells that harbour all hallmarks of HSCs, the reprogramming efficiency was still very low (~0.6%).…”

“…Recent work on the heterogeneous origin of the cells that comprise adult blood vessel endothelium may offer some clues to explain such a low reprogramming rate. In Plein et al, the vasculature of the embryo is shown to develop from two distinct lineages: in addition to mesoderm-derived ECs, the authors observed that a complementary source of endothelium is recruited into the pre-existing vasculature through transdifferentiation of erythro-myeloid progenitors (EMPs) that emerge in the yolk sac [32]. This distinct lineage persists into adulthood, raising the possibility that vascular endothelium acts as a functional mosaic, where a distinct lineage may be more amenable to haematopoietic reprogramming than others.…”