Arterial-venous endothelial cell fate is related to vascular endothelial growth factor and Notch status during human bone mesenchymal stem cell differentiation.
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.
Zhang
Gang
G
Department of Cardiac Surgery, Shandong Provincial Hospital, Shandong University, Jingwu Road 324, Jinan, PR China.
Zhou
Jianye
J
Fan
Quanxin
Q
Zheng
Zhe
Z
Zhang
Fusheng
F
Liu
Xuebin
X
Hu
Shengshou
S
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
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