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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.
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http://dx.doi.org/10.1038/s41467-024-44780-8 | DOI Listing |
Hum Reprod Update
September 2025
Faculty of Medicine, Paris Cité University, Paris, France.
Background: Infertility is a growing global challenge, with ARTs significantly improving birth rates for infertile couples. However, ART conceptions are associated with a higher risk of negative obstetrical and perinatal outcomes, with potential long-term effects on offspring health. Many pre-implantation embryos exhibit abnormal morphokinetics, implantation failure, or arrested development.
View Article and Find Full Text PDFDevelopment
September 2025
Department of Developmental Biology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
CCR7 chemokine G protein-coupled receptor is expressed in extraembryonic tissues of the early human embryo, including trophectoderm and its derivatives cytotrophoblast (CTB), extravillous trophoblast (EVT), and syncytiotrophoblast (STB). However, its function in placentation remains understudied. Here, we generated human embryonic stem cells harboring CCR7 deletions and differentiated them into human trophoblast stem cells (hTSC), their EVT and STB derivatives, and trophoblast organoids.
View Article and Find Full Text PDFStem Cell Reports
September 2025
Department of Physiology II, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; Department of Genome Biology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address:
Naive and primed states represent distinct phases of pluripotency during early embryonic development, both of which can be captured and interconverted in vitro. To understand pluripotency regulation, we performed a recessive genetic screen using homozygous mutant mouse embryonic stem cells (mESCs) and identified N-myristoyltransferase (NMT) as a novel regulator. Disruption of Nmt1 in mESCs conferred resistance to differentiation, and NMT suppression in mouse epiblast stem cells (mEpiSCs) promoted the conversion from the primed to the naive state.
View Article and Find Full Text PDFJ Cell Sci
August 2025
Institute of Medical Sciences, Foresterhill Health Campus, University of Aberdeen, AB25 2ZD, UK.
Embryonic stem cell research has uncovered different requirements for WNT/β-catenin signalling in human naïve pluripotent cells compared to the mouse paradigm. It is therefore important to study WNT/β-catenin signalling directly in models that recapitulate early human development. Since TCF/LEF factors mediate regulation of target genes downstream of WNT/β-catenin signalling, we examined the regulation, expression and protein localisation of the four TCF/LEF genes by analysing in vitro "snapshots" of human development, leveraging naïve and primed pluripotent cells, blastoids and preimplantation blastocysts.
View Article and Find Full Text PDFJ Assist Reprod Genet
August 2025
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.
Purpose: This study aimed to investigate the effects of repeated vitrification and trophectoderm (TE) biopsy procedures during preimplantation genetic testing (PGT) on blastocyst developmental potential and clinical outcomes.
Methods: This retrospective study analyzed data from January 2018 to January 2024. The study group included 229 blastocysts from 85 patients that underwent double vitrification (with either single or double biopsy).