title: Arterial-venous endothelial cell fate is related to vascular endothelial growth factor and Notch status during human bone mesenchymal stem cell differentiation.
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.
authors.affiliation: Department of Cardiac Surgery, Shandong Provincial Hospital, Shandong University, Jingwu Road 324, Jinan, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhang
authors.forename: Jianye
authors.initials: J
authors.lastname: Zhou
authors.forename: Quanxin
authors.initials: Q
authors.lastname: Fan
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zheng
authors.forename: Fusheng
authors.initials: F
authors.lastname: Zhang
authors.forename: Xuebin
authors.initials: X
authors.lastname: Liu
authors.forename: Shengshou
authors.initials: S
authors.lastname: Hu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D001158:Arteries / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology; D051837:COUP Transcription Factor II / Q000235:genetics; D002135:Calcium-Binding Proteins; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D036388:Ephrin-B2 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D036224:Receptor, EphB4 / Q000235:genetics; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000502:physiology*; D014680:Veins / Q000166:cytology* / Q000378:metabolism / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053829:Amyloid Precursor Protein Secretases; D051837:COUP Transcription Factor II; D002135:Calcium-Binding Proteins; D036388:Ephrin-B2; D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D036224:Receptor, EphB4; D000074562:Receptor, Notch4; D051880:Receptors, Notch; D042461:Vascular Endothelial Growth Factor A; C424126:DLL4 protein, human; C106075:NOTCH4 protein, human; C467484:VEGFA protein, human; C095569:NR2F2 protein, human