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YAP inhibition promotes endothelial cell differentiation from pluripotent stem cell through EC master transcription factor FLI1.

Authors
  • Quan, Yingyi1
  • Shan, Xiaoqiong2
  • Hu, Minjie1
  • Jin, Peifeng3
  • Ma, Jianshe1
  • Fan, Junming1
  • Yang, Jiwen1
  • Zhang, Huan1
  • Fan, Xiaofang1
  • Gong, Yongsheng1
  • Li, Ming4
  • Wang, Yongyu5
  • 1 Institute of Hypoxia Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325015, Zhejiang, China. , (China)
  • 2 The Third People's Hospital of Hangzhou. Hangzhou 310009, Zhejiang, China. , (China)
  • 3 Department of Cardiothoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, Zhejiang, China. , (China)
  • 4 Cardiac Regeneration Research Institute, School of Basic Medical Science, Wenzhou Medical University, Wenzhou 325015, Zhejiang, China. Electronic address: [email protected] , (China)
  • 5 Institute of Hypoxia Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325015, Zhejiang, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Journal of Molecular and Cellular Cardiology
Publisher
Elsevier
Publication Date
Feb 01, 2022
Volume
163
Pages
81–96
Identifiers
DOI: 10.1016/j.yjmcc.2021.10.004
PMID: 34666000
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Endothelial cells (ECs) derived from pluripotent stem cells (PSCs) provide great resource for vascular disease modeling and cell-based regeneration therapy. However, the molecular mechanisms of EC differentiation are not completely understood. In this study, we checked transcriptional profile by microarray and found Hippo pathway is changed and the activity of YAP decreased during mesoderm-mediated EC differentiation from human embryonic stem cells (hESCs). Knockdown of YAP in hESCs promoted both mesoderm and EC differentiation indicating by mesodermal- or EC-specific marker gene expression increased both in mRNA and protein level. In contrast, overexpression of YAP inhibited mesoderm and EC differentiation. Microarray data showed that several key transcription factors of EC differentiation, such as FLI1, ERG, SOX17 are upregulated. Interestingly, knockdown YAP enhanced the expression of these master transcription factors. Bioinformation analysis revealed that TEAD, a YAP binds transcription factors, might regulate the expression of EC master TFs, including FLI1. Luciferase assay confirmed that YAP binds to TEAD1, which would inhibit FLI1 expression. Finally, FLI1 overexpression rescued the effects of YAP overexpression-mediated inhibition of EC differentiation. In conclusion, we revealed the inhibitory effects of YAP on EC differentiation from PSCs, and YAP inhibition might promote expression of master TFs FLI1 for EC commitment through interacting with TEAD1, which might provide an idea for EC differentiation and vascular regeneration via manipulating YAP signaling. Copyright © 2021 Elsevier Ltd. All rights reserved.

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