Human trophoblast differentiation
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ABSTRACT:
PROVIDER: PRJNA717066 | ENA |
REPOSITORIES: ENA
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Project description:This study aims to compare in vivo human trophoblast differentiation into EVTs to different in vitro trophoblast organoids using single-cell and single-nuclei RNA sequencing. The study includes two type of systems: human primary trophoblast organoids (PTO) and trophoblast stem cells (TSCs). Trophoblast stem cell (TSC) lines BTS5 and BTS11 derived by Okae and colleagues were grown as described previously (Okae et al. 2018) and together with EVT media. Primary trophoblast organoids (PTO) were grown and differentiated into EVT as previously described by Turco & Sheridan (Turco et al 2018; Sheridan et al 2020). This study shows that the main regulatory programs mediating EVT invasion in vivo are preserved in in vitro models of EVT differentiation from primary trophoblast organoids and trophoblast stem cells.
2023-02-09 | E-MTAB-12650 | biostudies-arrayexpress
Project description:Comprehensive quantitative proteomic study of human pre-implantation embryo stages reveal dynamic proteome landscape from M2, 8-cell and blastocyst stage, and during trophoblast stem cell (TS) differentiation. Identified key factors in early human embryos and lineage-specific trophoblast proteome profiles, correlated with transcriptomic analyses. This direct proteomic analysis provides a comprehensive analysis of the dynamic protein expression in human embryos during pre-implantation development and a powerful resource to enable further mechanistic studies on human trophoblast development and function.
2023-07-05 | MSV000092349 | MassIVE
Project description:Early placenta development involves cytotrophoblast differentiation into extravillous trophoblast (EVT) and syncytiotrophoblast (STB). Defective trophoblast development and function may result in severe pregnancy complications, including fetal growth restriction and pre-eclampsia. The incidence of these complications is increased in pregnancies of fetuses affected by Rubinstein–Taybi syndrome, a developmental disorder predominantly caused by heterozygous mutations in CREB-binding protein (CREBBP) or E1A-binding protein p300 (EP300). Although the acetyltransferases CREBBP and EP300 are paralogs with many overlapping functions, the increased incidence of pregnancy complications is specific for EP300 mutations. We hypothesized that these complications have their origin in early placentation and that EP300 is involved in that process. Therefore, we investigated the role of EP300 and CREBBP in trophoblast differentiation, using human trophoblast stem cells (TSCs) and trophoblast organoids. We found that pharmacological CREBBP/EP300 inhibition blocks differentiation of TSCs into both EVT and STB lineages, and results in an expansion of TSC-like cells under differentiation-inducing conditions. Specific targeting by RNA interference or CRISPR/Cas9-mediated mutagenesis demonstrated that knockdown of EP300 but not CREBBP, inhibits trophoblast differentiation, consistent with the complications seen in Rubinstein–Taybi syndrome pregnancies. By transcriptome sequencing, we identified transforming growth factor alpha (TGFA, encoding TGF-α) as being strongly upregulated upon EP300 knockdown. Moreover, supplementing differentiation medium with TGF-α, which is a ligand for the epidermal growth factor receptor (EGFR), likewise affected trophoblast differentiation and resulted in increased TSC-like cell proliferation. These findings suggest that EP300 facilitates trophoblast differentiation by interfering with at least EGFR signaling, pointing towards a crucial role for EP300 in early human placentation.
2023-12-19 | GSE250424 | GEO
Project description:Identification of genes involved in trophoblast differentiation is of great interest in understanding cellular and molecular mechanisms involved in placental development and is relevant clinically to fetal development, fertility, and maternal health. To understand, on a global scale, changes in the transcriptome during the differentiation of hESCs down the trophoblast lineage, a large-scale microarray analysis was performed. This work provides an in vitro functional genomic model with which to identify genes involved in trophoblast development. We investigated differentiation of human embryonic stemcells (hESCs) down the trophoblast lineage by culture with bone morphogenetic protein 4 (BMP4) over a 10-day period and analyze the cell every 2-days.
2011-09-16 | E-GEOD-30915 | biostudies-arrayexpress
Project description: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 placental development remains poorly explored. Here, we generated human embryonic stem cells harboring CCR7 deletions and differentiated them into human trophoblast stem cell (hTSC) and hTSC-derived trophoblast organoids. We found that CCR7 mutant EVTs retained hTSC-like characteristics, exhibited decreased epithelial-to-mesenchymal transition, and reduced cell motility. Additionally, CCL21-CCR7 induced EVT terminal differentiation into endovascular EVT-like cells. Transcriptional profiling in CCR7 KO STBs identified reduced viral defense gene expression related to the protection against maternal-fetal transmission. Investigation of trophoblast organoids using single cell transcriptome profiling showed that CCR7 mutant trophoblast organoids comprised a smaller EVT population, but a larger STB population, compared to wild type organoids, while CellChat analysis indicated altered cell-cell communication including WNT, ACTIVIN, and IFN-I signaling pathways. Mechanistically, we found that CCR7 limited the cell-cell fusion of early STB differentiation by reducing cAMP levels. Together, our studies demonstrate that CCR7 plays multiple roles in cellular decision-making during trophoblast differentiation, promoting EVT differentiation, and limiting cell-cell fusion during early STB differentiation.
2025-08-31 | GSE275552 | GEO
Project description: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 placental development remains poorly explored. Here, we generated human embryonic stem cells harboring CCR7 deletions and differentiated them into human trophoblast stem cell (hTSC) and hTSC-derived trophoblast organoids. We found that CCR7 mutant EVTs retained hTSC-like characteristics, exhibited decreased epithelial-to-mesenchymal transition, and reduced cell motility. Additionally, CCL21-CCR7 induced EVT terminal differentiation into endovascular EVT-like cells. Transcriptional profiling in CCR7 KO STBs identified reduced viral defense gene expression related to the protection against maternal-fetal transmission. Investigation of trophoblast organoids using single cell transcriptome profiling showed that CCR7 mutant trophoblast organoids comprised a smaller EVT population, but a larger STB population, compared to wild type organoids, while CellChat analysis indicated altered cell-cell communication including WNT, ACTIVIN, and IFN-I signaling pathways. Mechanistically, we found that CCR7 limited the cell-cell fusion of early STB differentiation by reducing cAMP levels. Together, our studies demonstrate that CCR7 plays multiple roles in cellular decision-making during trophoblast differentiation, promoting EVT differentiation, and limiting cell-cell fusion during early STB differentiation.
2025-09-02 | GSE274397 | GEO
Project description:Histone Demethylases and Trophoblast Differentiation
| PRJNA742443 | ENA
Project description:Manifold roles of CCR7 chemokine GPCR in human trophoblast differentiation
| PRJNA1146339 | ENA
Project description:Manifold roles of CCR7 chemokine GPCR in human trophoblast differentiation
| PRJNA1151661 | ENA
Project description:Dynamics of Trophoblast Differentiation in Peri-implantation Stage Human Embryos
| PRJNA534673 | ENA