VGLL4 promotes vascular endothelium specification via TEAD1 in the vascular organoids and human pluripotent stem cells-derived endothelium model.

Yingyi Quan, Minjie Hu, Jiang Jiang, Peifeng Jin, Junming Fan, Ming Li, Xiaofang Fan, Yongsheng Gong, Yang Yang, Yongyu Wang

Cellular and molecular life sciences : CMLS 2023 Jul 19

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We have shown that Hippo-YAP signaling pathway plays an important role in endothelial cell differentiation. Vestigial-like family member 4 (VGLL4) has been identified as a YAP inhibitor. However, the exact function of VGLL4 in vascular endothelial cell development remains unclear. In this study, we investigated the role of VGLL4, in human endothelial lineage specification both in 3D vascular organoid and 2D endothelial cell differentiation. In this study, we found that VGLL4 was increased during 3D vascular organoids generation and directed differentiation of human embryonic stem cells H1 towards the endothelial lineage. Using inducible ectopic expression of VGLL4 based on the piggyBac system, we proved that overexpression of VGLL4 in H1 promoted vascular organoids generation and endothelial cells differentiation. In contrast, VGLL4 knockdown (heterozygous knockout) of H1 exhibited inhibitory effects. Using bioinformatics analysis and protein immunoprecipitation, we further found that VGLL4 binds to TEAD1 and facilitates the expression of endothelial master transcription factors, including FLI1, to promote endothelial lineage specification. Moreover, TEAD1 overexpression rescued VGLL4 knockdown-mediated negative effects. In summary, VGLL4 promotes EC lineage specification both in 3D vascular organoid and 2D EC differentiation from pluripotent stem cell, VGLL4 interacts with TEAD1 and facilitates EC key transcription factor, including FLI1, to enhance EC lineage specification. © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Citation

Yingyi Quan, Minjie Hu, Jiang Jiang, Peifeng Jin, Junming Fan, Ming Li, Xiaofang Fan, Yongsheng Gong, Yang Yang, Yongyu Wang. VGLL4 promotes vascular endothelium specification via TEAD1 in the vascular organoids and human pluripotent stem cells-derived endothelium model. Cellular and molecular life sciences : CMLS. 2023 Jul 19;80(8):215