Transcription factor TEAD1 is essential for vascular development by promoting vascular smooth muscle differentiation

Tong Wen, Jinhua Liu, Xiangqin He, Kunzhe Dong, Guoqing Hu, Luyi Yu, Qin Yin, Islam Osman, Jingtian Peng, Zeqi Zheng, Hongbo Xin, David J Fulton, Quansheng Du, Wei Zhang, Jiliang Zhou

Research output: Contribution to journalArticle

Abstract

TEAD1 (TEA domain transcription factor 1), a transcription factor known for the functional output of Hippo signaling, is important for tumorigenesis. However, the role of TEAD1 in the development of vascular smooth muscle cell (VSMC) is unknown. To investigate cell-specific role of Tead1, we generated cardiomyocyte (CMC) and VSMC-specific Tead1 knockout mice. We found CMC/VSMC-specific deletion of Tead1 led to embryonic lethality by E14.5 in mice due to hypoplastic cardiac and vascular walls, as a result of impaired CMC and VSMC proliferation. Whole transcriptome analysis revealed that deletion of Tead1 in CMCs/VSMCs downregulated expression of muscle contractile genes and key transcription factors including Pitx2c and myocardin. In vitro studies demonstrated that PITX2c and myocardin rescued TEAD1-dependent defects in VSMC differentiation. We further identified Pitx2c as a novel transcriptional target of TEAD1, and PITX2c exhibited functional synergy with myocardin by directly interacting with myocardin, leading to augment the differentiation of VSMC. In summary, our study reveals a critical role of Tead1 in cardiovascular development in mice, but also identifies a novel regulatory mechanism, whereby Tead1 functions upstream of the genetic regulatory hierarchy for establishing smooth muscle contractile phenotype.

Original languageEnglish (US)
JournalCell Death and Differentiation
DOIs
StatePublished - Jan 1 2019

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Vascular Smooth Muscle
Smooth Muscle Myocytes
Blood Vessels
Transcription Factors
Cardiac Myocytes
Gene Expression Profiling
Knockout Mice
Smooth Muscle
Cell Differentiation
Carcinogenesis
Down-Regulation
Cell Proliferation
Phenotype
Muscles
myocardin
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Transcription factor TEAD1 is essential for vascular development by promoting vascular smooth muscle differentiation. / Wen, Tong; Liu, Jinhua; He, Xiangqin; Dong, Kunzhe; Hu, Guoqing; Yu, Luyi; Yin, Qin; Osman, Islam; Peng, Jingtian; Zheng, Zeqi; Xin, Hongbo; Fulton, David J; Du, Quansheng; Zhang, Wei; Zhou, Jiliang.

In: Cell Death and Differentiation, 01.01.2019.

Research output: Contribution to journalArticle

Wen, Tong ; Liu, Jinhua ; He, Xiangqin ; Dong, Kunzhe ; Hu, Guoqing ; Yu, Luyi ; Yin, Qin ; Osman, Islam ; Peng, Jingtian ; Zheng, Zeqi ; Xin, Hongbo ; Fulton, David J ; Du, Quansheng ; Zhang, Wei ; Zhou, Jiliang. / Transcription factor TEAD1 is essential for vascular development by promoting vascular smooth muscle differentiation. In: Cell Death and Differentiation. 2019.
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abstract = "TEAD1 (TEA domain transcription factor 1), a transcription factor known for the functional output of Hippo signaling, is important for tumorigenesis. However, the role of TEAD1 in the development of vascular smooth muscle cell (VSMC) is unknown. To investigate cell-specific role of Tead1, we generated cardiomyocyte (CMC) and VSMC-specific Tead1 knockout mice. We found CMC/VSMC-specific deletion of Tead1 led to embryonic lethality by E14.5 in mice due to hypoplastic cardiac and vascular walls, as a result of impaired CMC and VSMC proliferation. Whole transcriptome analysis revealed that deletion of Tead1 in CMCs/VSMCs downregulated expression of muscle contractile genes and key transcription factors including Pitx2c and myocardin. In vitro studies demonstrated that PITX2c and myocardin rescued TEAD1-dependent defects in VSMC differentiation. We further identified Pitx2c as a novel transcriptional target of TEAD1, and PITX2c exhibited functional synergy with myocardin by directly interacting with myocardin, leading to augment the differentiation of VSMC. In summary, our study reveals a critical role of Tead1 in cardiovascular development in mice, but also identifies a novel regulatory mechanism, whereby Tead1 functions upstream of the genetic regulatory hierarchy for establishing smooth muscle contractile phenotype.",
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