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  • Title: Arterial-venous endothelial cell fate is related to vascular endothelial growth factor and Notch status during human bone mesenchymal stem cell differentiation.
    Author: Zhang G, Zhou J, Fan Q, Zheng Z, Zhang F, Liu X, Hu S.
    Journal: FEBS Lett; 2008 Aug 20; 582(19):2957-64. PubMed ID: 18671974.
    Abstract:
    Human bone mesenchymal stem cells (hMSCs) can differentiate into endothelial cells (ECs), so we aimed to investigate whether hMSCs could also differentiate into a specific arterial or venous ECs. hMSCs were induced to differentiate into ECs using vascular endothelial growth factor (VEGF). Low VEGF concentration (50 ng/ml) upregulated the venous marker gene EphB4, however high concentration (100 ng/ml) upregulated the arterial marker genes ephrinB2, Dll4 and Notch4, and downregulated the venous marker genes EphB4 and COUP-TFll. This VEGF dose-dependent induction was largely blocked by inhibition of the Notch pathway in hMSCs treated with gamma-secretase inhibitor. Therefore, differentiation of hMSCs into arterial- or venous-specific ECs depends on VEGF and is regulated by the Notch pathway.
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