VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification

Yueli Yang, Wenqi Jia, Zhiwei Luo, Yunpan Li, Hao Liu, Lixin Fu, Jinxiu Li, Yu Jiang, Junjian Lai, Haiwei Li, Babangida Jabir Saeed, Yi Zou, Yuan Lv, Liang Wu, Ting Zhou, Yongli Shan, Chuanyu Liu, Yiwei Lai, Longqi Liu, Andrew P. Hutchins, Miguel A. Esteban (), Md. Abdul Mazid () and Wenjuan Li ()
Additional contact information
Yueli Yang: Jilin University
Wenqi Jia: Chinese Academy of Sciences (CAS)
Zhiwei Luo: Chinese Academy of Sciences (CAS)
Yunpan Li: Chinese Academy of Sciences (CAS)
Hao Liu: Chinese Academy of Sciences (CAS)
Lixin Fu: University of Chinese Academy of Sciences
Jinxiu Li: University of Chinese Academy of Sciences
Yu Jiang: Jilin University
Junjian Lai: Chinese Academy of Sciences (CAS)
Haiwei Li: Guangzhou Medical University
Babangida Jabir Saeed: Chinese Academy of Sciences (CAS)
Yi Zou: BGI Research
Yuan Lv: Chinese Academy of Sciences (CAS)
Liang Wu: Chinese Academy of Sciences (CAS)
Ting Zhou: Sloan Kettering Institute
Yongli Shan: Guangzhou Institutes of Biomedicine and Health
Chuanyu Liu: BGI Research
Yiwei Lai: BGI Research
Longqi Liu: BGI Research
Andrew P. Hutchins: Southern University of Science and Technology
Miguel A. Esteban: Jilin University
Md. Abdul Mazid: Chinese Academy of Sciences (CAS)
Wenjuan Li: Chinese Academy of Sciences (CAS)

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract In contrast to rodents, the mechanisms underlying human trophectoderm and early placenta specification are understudied due to ethical barriers and the scarcity of embryos. Recent reports have shown that human pluripotent stem cells (PSCs) can differentiate into trophectoderm (TE)-like cells (TELCs) and trophoblast stem cells (TSCs), offering a valuable in vitro model to study early placenta specification. Here, we demonstrate that the VGLL1 (vestigial-like family member 1), which is highly expressed during human and non-human primate TE specification in vivo but is negligibly expressed in mouse, is a critical regulator of cell fate determination and self-renewal in human TELCs and TSCs derived from naïve PSCs. Mechanistically, VGLL1 partners with the transcription factor TEAD4 (TEA domain transcription factor 4) to regulate chromatin accessibility at target gene loci through histone acetylation and acts in cooperation with GATA3 and TFAP2C. Our work is relevant to understand primate early embryogenesis and how it differs from other mammalian species.

Date: 2024
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DOI: 10.1038/s41467-024-44780-8

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