VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification

• Published in: Nature communications Vol. 15; no. 1; pp. 583 - 18
• Main Authors: Yang, Yueli, Jia, Wenqi, Luo, Zhiwei, Li, Yunpan, Liu, Hao, Fu, Lixin, Li, Jinxiu, Jiang, Yu, Lai, Junjian, Li, Haiwei, Saeed, Babangida Jabir, Zou, Yi, Lv, Yuan, Wu, Liang, Zhou, Ting, Shan, Yongli, Liu, Chuanyu, Lai, Yiwei, Liu, Longqi, Hutchins, Andrew P., Esteban, Miguel A., Mazid, Md. Abdul, Li, Wenjuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/100; 14/63; 38; 38/88; 38/89; 38/90; 38/91; 631/136/142; 631/532/2064; 631/532/2441; Accessibility; Acetylation; Animals; Cell differentiation; Cell Differentiation - genetics; Cell fate; Cell Lineage - genetics; Cell self-renewal; Chromatin; Cooperation; DNA-Binding Proteins - genetics; Embryogenesis; Embryonic growth stage; Female; GATA-3 protein; Histones; Humanities and Social Sciences; Humans; Mammals; Mice; multidisciplinary; Placenta; Pluripotency; Pluripotent Stem Cells; Pregnancy; Primates; Science; Science (multidisciplinary); Specifications; Stem cells; TEA Domain Transcription Factors; Transcription factors; Transcription Factors - genetics; Trophectoderm; Trophoblasts - physiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-44780-8

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. Authors report that VGLL1 regulates cell fate determination and self-renewal of human pluripotent stem cell-derived trophectoderm-like cells and trophoblast stem cells via modulation of chromatin accessibility in cooperation with TEAD4.