VGLL4-TEAD1 promotes vascular smooth muscle cell differentiation from human pluripotent stem cells via TET2

doi:10.1016/j.yjmcc.2023.01.005

科研成果详情

题名	VGLL4-TEAD1 promotes vascular smooth muscle cell differentiation from human pluripotent stem cells via TET2
作者	Wang, Zuxuan1; Quan, Yingyi 1; Hu, Minjie1; Xu, Yubin1; Chen, Yuhao1; Jin, Peifeng2; Ma, Jianshe1; Chen, Xiufang3; Fan, Junming1; Fan, Xiaofang1; Gong, Yongsheng1; Li, Ming3; Wang, Yongyu1,3
发表日期	2023-03
发表期刊	Journal of molecular and cellular cardiology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Cell differentiation Pluripotent stem cells TEA domain transcription factor 1 (TEAD1) Ten-eleven-translocation 2 (TET2) Vascular smooth muscle cell Vestigial-like family member 4 (VGLL4)
其他关键词	TRANSCRIPTION FACTOR TEAD1 ; TUMOR-SUPPRESSOR ; VGLL4 ; METHYLATION ; GENERATION ; REGULATOR ; MYOCARDIN ; ENZYMES ; CANCER
摘要	The Hippo signaling pathway plays a critical role in cardiovascular development and stem cell differentiation. Using microarray profiling, we found that the Hippo pathway components vestigial-like family member 4 (VGLL4) and TEA domain transcription factor 1 (TEAD1) were upregulated during vascular smooth muscle cell (VSMC) differentiation from H1 ESCs (H1 embryonic stem cells). To further explore the role and molecular mechanisms of VGLL4 in regulating VSMC differentiation, we generated a VGLL4-knockdown H1 ESC line (heterozygous knockout) using the CRISPR/Cas9 system and found that VGLL4 knockdown inhibited VSMC specification. In contrast, overexpression of VGLL4 using the PiggyBac transposon system facilitated VSMC differentiation. We confirmed that this effect was mediated via TEAD1 and VGLL4 interaction. In addition, bioinformatics analysis revealed that Ten-eleven-translocation 2 (TET2), a DNA dioxygenase, is a target of TEAD1, and a luciferase assay further verified that TET2 is the target of the VGLL4-TEAD1 complex. Indeed, TET2 overexpression promoted VSMC marker gene expression and countered the VGLL4 knockdown-mediated inhibitory effects on VSMC differentiation. In summary, we revealed a novel role of VGLL4 in promoting VSMC differentiation from hESCs and identified TET2 as a new target of the VGLL4-TEAD1 complex, which may demethylate VSMC marker genes and facilitate VSMC differentiation. This study provides new insights into the VGLL4-TEAD1-TET2 axis in VSMC differentiation and vascular development.
资助项目	Natural Science Foundation of Zhejiang Province [LY21C120003]; National Natural Science Foundation of China [82070487, 81670454]; Scientific Research Start-up Fund of Wenzhou Medical University [QTJ15029]
出版者	ELSEVIER SCI LTD
ISSN	0022-2828
EISSN	1095-8584
卷号	176 页码:21-32
DOI	10.1016/j.yjmcc.2023.01.005
页数	12
WOS类目	Cardiac & Cardiovascular Systems ; Cell Biology
WOS研究方向	Cardiovascular System & Cardiology ; Cell Biology
WOS记录号	WOS:000926016100001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2023-01
URL	查看原文
PubMed ID	36657637
SCOPUSEID	2-s2.0-85146880733
通讯作者地址	[Wang, Yongyu]Institute of Hypoxia Medicine,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325015,China
Scopus学科分类	Molecular Biology;Cardiology and Cardiovascular Medicine
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/172448
专题	基础医学院（机能实验教学中心）附属第一医院
通讯作者	Wang, Yongyu
作者单位	1.Institute of Hypoxia Medicine,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325015,China; 2.Department of Cardiothoracic Surgery,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325015,China; 3.Cardiac Regeneration Research Institute,School of Basic Medical Science,Wenzhou Medical University,Zhejiang,Wenzhou,325015,China
第一作者单位	基础医学院（机能实验教学中心）
通讯作者单位	基础医学院（机能实验教学中心）
第一作者的第一单位	基础医学院（机能实验教学中心）
推荐引用方式 GB/T 7714	Wang, Zuxuan,Quan, Yingyi,Hu, Minjie,et al. VGLL4-TEAD1 promotes vascular smooth muscle cell differentiation from human pluripotent stem cells via TET2[J]. Journal of molecular and cellular cardiology,2023,176:21-32.
APA	Wang, Zuxuan., Quan, Yingyi., Hu, Minjie., Xu, Yubin., Chen, Yuhao., ... & Wang, Yongyu. (2023). VGLL4-TEAD1 promotes vascular smooth muscle cell differentiation from human pluripotent stem cells via TET2. Journal of molecular and cellular cardiology, 176, 21-32.
MLA	Wang, Zuxuan,et al."VGLL4-TEAD1 promotes vascular smooth muscle cell differentiation from human pluripotent stem cells via TET2".Journal of molecular and cellular cardiology 176(2023):21-32.