Role in formation of vascular system

The two lineages arising from the EPC and the hematopoietic progenitor cell (HPC) form the blood circulatory system. Hematopoietic stem cells can of course undergo self-renewal, and are multipotent cells that give rise to erythrocytes (red blood cells), megakaryocytes/platelets, mast cells, T-lymphocytes, B-lymphocytes, dendritic cells, natural killer cells, monocyte/macrophage, and granulocytes.  A study found that in the beginning stages of mouse embryogenesis, commencing at embryonic day 7.5, HPCs are produced close to the emerging vascular system. In the yolk sac’s blood islands, HPCs and EC lineages emerge from the extraembryonic mesoderm in near unison. This creates a formation in which early erythrocytes are enveloped by angioblasts, and together they give rise to mature ECs. This observation gave rise to the hypothesis that the two lineages come from the same precursor, termed hemangioblast. Even though there is evidence that corroborates a hemangioblast, the isolation and exact location in the embryo has been difficult to pinpoint. Some researchers have found that cells with hemangioblast properties have been located in the posterior end of the primitive streak during gastrulation.

In 1917, Florence Sabin first observed the development of blood vessels and red blood cells in the yolk sac of chick embryos occur in close proximity and time. Then, in 1932, Murray detected the same event and created the term “hemangioblast” for what Sabin had seen.

Further evidence to corroborate hemangioblasts come from the expression of various genes such as CD34 and Tie2 by both lineages. The fact that this expression was seen in both EC and HPC lineages led researchers to propose a common origin. However, endothelial markers like Flk1/VEGFR-2 is exclusive to ECs but stops HPCs from progressing into an EC. It is accepted that VEGFR-2+ cells are a common precursor for HPCs and ECs. If the Vegfr3 gene is deleted then both HPC and EC differentiation comes to a halt in embryos. VEGF promotes angioblast differentiation; whereas, VEGFR-1 stops the hemangioblast from becoming an EC. In addition, basic fibroblast growth factor FGF-2 is also involved in promoting angioblasts from the mesoderm. After angioblasts commit to becoming an EC, the angioblasts gather and rearrange to assemble in a tube similar to a capillary. Angioblasts can travel during the formation of the circulatory system to configure the branches to allow for directional blood flow. Pericytes and smooth muscle cells encircle ECs when they are differentiating into arterial or venous arrangements. Surrounding the ECs creates a brace to help stabilize the vessels known as the pericellular basal lamina. It is suggested pericytes and smooth muscle cells come from neural crest cells and the surrounding mesenchyme.