PMID- 31827524 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1687-966X (Print) IS - 1687-9678 (Electronic) VI - 2019 DP - 2019 TI - Shear Stress Promotes Arterial Endothelium-Oriented Differentiation of Mouse-Induced Pluripotent Stem Cells. PG - 1847098 LID - 10.1155/2019/1847098 [doi] LID - 1847098 AB - Establishment of a functional vascular network, which is required in tissue repair and regeneration, needs large-scale production of specific arterial or venous endothelial cells (ECs) from stem cells. Previous in vitro studies by us and others revealed that shear stress induces EC differentiation of bone marrow-derived mesenchymal stem cells and embryonic stem cells. In this study, we focused on the impact of different magnitudes of shear stress on the differentiation of mouse-induced pluripotent stem cells (iPSCs) towards arterial or venous ECs. When iPSCs were exposed to shear stress (5, 10, and 15 dyne/cm(2)) with 50 ng/mL vascular endothelial growth factor and 10 ng/mL fibroblast growth factor, the expression levels of the general EC markers and the arterial markers increased, and the stress amplitude of 10 dyne/cm(2) could be regarded as a proper promoter, whereas the venous and lymphatic markers had little or no expression. Further, shear stress caused cells to align parallel to the direction of the flow, induced cells forming functional tubes, and increased the secretion of nitric oxide. In addition, Notch1 was significantly upregulated, and the Notch ligand Delta-like 4 was activated in response to shear stress, while inhibition of Notch signaling by DAPT remarkably abolished the shear stress-induced arterial epithelium differentiation. Taken together, our results indicate that exposure to appropriate shear stress facilitated the differentiation of mouse iPSCs towards arterial ECs via Notch signaling pathways, which have potential applications for both disease modeling and regenerative medicine. CI - Copyright (c) 2019 Yan Huang et al. FAU - Huang, Yan AU - Huang Y AD - Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. AD - Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China. FAU - Chen, Xiaofang AU - Chen X AUID- ORCID: 0000-0003-2058-5731 AD - Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. AD - Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China. FAU - Che, Jifei AU - Che J AD - Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. FAU - Zhan, Qi AU - Zhan Q AD - Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. FAU - Ji, Jing AU - Ji J AD - Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. AD - Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China. FAU - Fan, Yubo AU - Fan Y AUID- ORCID: 0000-0002-3480-4395 AD - Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. AD - Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China. AD - Beijing Key Laboratory of Rehabilitation Technical Aids for Old-Age Disability, National Research Center for Rehabilitation Technical Aids, Beijing 100176, China. LA - eng PT - Journal Article DEP - 20191115 PL - United States TA - Stem Cells Int JT - Stem cells international JID - 101535822 PMC - PMC6881757 COIS- The authors declare to have no conflicts of interests. EDAT- 2019/12/13 06:00 MHDA- 2019/12/13 06:01 PMCR- 2019/11/15 CRDT- 2019/12/13 06:00 PHST- 2019/01/31 00:00 [received] PHST- 2019/09/05 00:00 [revised] PHST- 2019/10/17 00:00 [accepted] PHST- 2019/12/13 06:00 [entrez] PHST- 2019/12/13 06:00 [pubmed] PHST- 2019/12/13 06:01 [medline] PHST- 2019/11/15 00:00 [pmc-release] AID - 10.1155/2019/1847098 [doi] PST - epublish SO - Stem Cells Int. 2019 Nov 15;2019:1847098. doi: 10.1155/2019/1847098. eCollection 2019.