International Journal of Stem Cells : eISSN 2005-5447

Fig. 1.

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Fig. 1. The development of vascular endothelial cells (ECs) in arteriovenous specification and angiogenesis. Vasculogenesis occurs as ECs emerge from mesodermal precursors that differentiate into angioblasts and vascular plexus. From primitive vascular plexus, ECs undergo arteriovenous specification and angiogenesis to form multitude of vascular networks (Left panel). Arterial and venous specification in developing vasculature is driven by Notch and COUP transcription factor 2 (COUP-TFII) signaling. High flow initiates Notch activation and induces downstream signals HEY/HES and EFNB2 for arterial priming. COUP-TFII primes vasculature toward venous and lymphatic vessels where downstream activation of EPHB4 leads to venous EC differentiation and vascular endothelial growth factor receptor 3 (VEGFR3) leads to lymphatic EC differentiation (Right upper panel). Angiogenesis initiates as tip cells are activated by gradient of VEGF signals that induces delta-like 4 (DLL4)/Notch pathway and initiates migration. The adjacent stalk cells receive notch signaling from tip cells and initiates proliferation for tube morphogenesis (Right lower panel).
International Journal of Stem Cells 2024;17:15-29 https://doi.org/10.15283/ijsc23086
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