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Updated: Jul 5, 2025

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Published on: August 10, 2022
VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification.
Yueli Yang1, Wenqi Jia2,3,4, Zhiwei Luo2,3
1State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.
Vestigial-like family member 1 (VGLL1) is crucial for human trophectoderm development and early placenta formation. This protein regulates cell fate and self-renewal in human stem cells, offering insights into primate embryogenesis.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Reproductive Biology
Background:
- Human trophectoderm and placenta specification mechanisms are poorly understood due to ethical and practical limitations.
- Human pluripotent stem cells (PSCs) offer a promising in vitro model for studying early placental development.
- Previous research indicates PSCs can differentiate into trophectoderm-like cells (TELCs) and trophoblast stem cells (TSCs).
Purpose of the Study:
- To investigate the role of VGLL1 (vestigial-like family member 1) in human trophectoderm and early placenta specification.
- To elucidate the molecular mechanisms by which VGLL1 regulates cell fate and self-renewal in human TELCs and TSCs.
- To compare primate early embryogenesis with other mammalian species.
Main Methods:
- Utilized human pluripotent stem cells (PSCs) differentiated into trophectoderm-like cells (TELCs) and trophoblast stem cells (TSCs).
- Investigated the expression and function of VGLL1 in these in vitro models.
- Analyzed VGLL1's interaction with transcription factors like TEAD4, GATA3, and TFAP2C.
- Examined VGLL1's role in regulating chromatin accessibility and histone acetylation at target gene loci.
Main Results:
- VGLL1 is highly expressed during human and non-human primate trophectoderm specification but not in mice.
- VGLL1 is a critical regulator of cell fate determination and self-renewal in human TELCs and TSCs derived from naïve PSCs.
- VGLL1 functions with TEAD4 to control chromatin accessibility via histone acetylation, cooperating with GATA3 and TFAP2C.
Conclusions:
- VGLL1 plays a vital role in human trophectoderm specification and early placenta formation.
- The findings highlight key differences between primate and rodent early embryogenesis.
- This study provides a valuable in vitro model for understanding human placental development and related disorders.
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