Effect and mechanism of hypoxia on differentiation of porcine-induced pluripotent stem cells into vascular endothelial cells

Pigs are similar to humans in organ size and physiological function, and are considered as good models for studying cardiovascular diseases. The study of porcine-induced pluripotent stem cells (piPSC) differentiating into vascular endothelial cells (EC) is expected to open up a new way of obtaining high-quality seed cells. Given that the hypoxic environment has an important role in the differentiation process of vascular EC, this work intends to establish a hypoxia-induced differentiation system of piPSC into vascular EC. There is evidence that the hypoxia microenvironment in the initial stage could significantly improve differentiation efficiency. Further study suggests that the hypoxia culture system supports a combined effect of hypoxia inducible factors and their associated regulatory molecules, such as HIF-1α, VEGFA, FGF2, LDH-A, and PDK1, which can efficiently promote the lineage-specific differentiation of piPSC into EC. Most notably, the high level of ETV2 after 4 d of hypoxic treatment indicates that it possibly plays an important role in the promoting process of EC differentiation. The research is expected to help the establishment of new platforms for piPSC directional induction research, so as to obtain adequate seed cells with ideal phenotype and functionality.