Human trophoblast differentiation is associated with profound genetic and epigenetic changes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE127288 | GEO | 2019/07/31
REPOSITORIES: GEO
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Project description:Human trophoblast differentiation is associated with profound genetic and epigenetic changes
| PRJNA524672 | ENA
Project description:Defective placental implantation and vascularization with accompanying hypoxia contribute to preeclampsia (PE), a leading cause of maternal and neonatal morbidity and mortality. Genetic and epigenetic mechanisms underlying differentiation of proliferative cytotrophoblasts (CytTs) to multinucleated syncytiotrophoblast (SynT) are incompletely defined. The SynT performs key functions in nutrient and gas exchange, hormone production, and protection of the fetus from rejection by the maternal immune system. In this study, we used chromatin immunoprecipitation sequencing of midgestation human trophoblasts before CytT and after SynT differentiation in primary culture to analyze changes in binding of RNA polymerase II (Pol II) and of active and repressive histone marks during SynT differentiation. Our findings reveal that increased Pol II binding to promoters of a subset of genes during trophoblast differentiation was closely correlated with active histone marks. This gene set was enriched in those controlling immune response and immune modulation, including interferon-induced tetratricopeptide repeat and placenta-specific glycoprotein gene family members. By contrast, genes downregulated during SynT differentiation included proinflammatory transcription factors ERG1, cFOS, and cJUN, as well as members of the NR4A orphan nuclear receptor subfamily, NUR77, NURR1, and NOR1. Downregulation of proinflammatory transcription factors upon SynT differentiation was associated with decreased promoter enrichment of endogenous H3K27Ac and H3K9Ac and enhanced binding of H3K9me3 and histone deacetylase 1. However, promoter enrichment of H3K27me3 was low in both CytT and SynT and was not altered with changes in gene expression. These findings provide important insight into mechanisms underlying human trophoblast differentiation and may identify therapeutic targets for placental disorders, such as PE.
| S-EPMC6821221 | biostudies-literature
Project description:We characterized the mouse trophoblast giant cell epigenome and gene expression profiles. We then compared these data to our data on underrepresentation in the polyploid trophoblast giant cells. We profiled 5 histone modifications (+ chromatin input) using ChIP-Seq, and digital expression profiles (3' RNA-Seq) for trophoblast giant cells derived from mouse. Furthermore, we profiled digital expression profiles (3' RNA-Seq) for in vivo trophoblast giant cells samples from e9.5 wildtype mouse trophoblast giant cells. We found that underrepresented domains in trophoblast giant cells are enriched for repressive marks and anti-correlate with active marks and transcription.
2014-05-29 | E-GEOD-50561 | biostudies-arrayexpress
Project description:To understand the human placenta development, we investigated the features of two trophoblast models, trophoblast organoids and trophoblast stem cells, with the aim of identifying which type of trophoblast in vivo they most closely resemble. To this end, we profiled the transcriptomes from the two models by using the Truseq stranded mRNA library kit (Illumina).
2021-10-18 | E-MTAB-10429 | biostudies-arrayexpress
Project description:The preimplantation development in eutherian mammals is diverse. However, ethical and technical constraints significantly limit our understanding of the molecular and biochemical pathways governing human development. In this study, we discovered an unexpected, species-specific epigenetic pathway regulated by H2A.J, a largely uncharacterized histone variant in preimplantation development using human Blastoid models, IVF bovine embryos, and in vitro human stem cell models. We discovered that H2A.J is expressed in human and bovine placentas, contrasting with its absence in mice, and that H2A.J is essential for trophoblast expansion and viability in human and bovine. Our findings also revealed that H2A.J is enriched at promoters and introns of genes and interacts with RNA Polymerase I and II and pro-elongation factors, thereby regulating RNA Polymerase elongation and trophoblast maintenance in human embryo development. This study sheds light on a novel chromatin factor crucial for proper development in humans and large mammals, offering insights into the evolution of preimplantation development in eutherians. Our research provides valuable insights into evolutionarily divergent epigenetic mechanisms and biological functions in trophoblast lineage maintenance and transcriptional regulation, laying the groundwork for future investigations into the essential but understudied process of human placentation.
2026-03-25 | GSE262629 | GEO
Project description:The preimplantation development in eutherian mammals is diverse. However, ethical and technical constraints significantly limit our understanding of the molecular and biochemical pathways governing human development. In this study, we discovered an unexpected, species-specific epigenetic pathway regulated by H2A.J, a largely uncharacterized histone variant in preimplantation development using human Blastoid models, IVF bovine embryos, and in vitro human stem cell models. We discovered that H2A.J is expressed in human and bovine placentas, contrasting with its absence in mice, and that H2A.J is essential for trophoblast expansion and viability in human and bovine. Our findings also revealed that H2A.J is enriched at promoters and introns of genes and interacts with RNA Polymerase I and II and pro-elongation factors, thereby regulating RNA Polymerase elongation and trophoblast maintenance in human embryo development. This study sheds light on a novel chromatin factor crucial for proper development in humans and large mammals, offering insights into the evolution of preimplantation development in eutherians. Our research provides valuable insights into evolutionarily divergent epigenetic mechanisms and biological functions in trophoblast lineage maintenance and transcriptional regulation, laying the groundwork for future investigations into the essential but understudied process of human placentation.
2026-03-25 | GSE262633 | GEO
Project description:To understand the human placenta development, we investigated the features of two trophoblast models, trophoblast organoids and trophoblast stem cells, with the aim of identifying which type of trophoblast in vivo they most closely resemble. To this end, we profiled the microRNAs from the two models by using the Bioo Nextflex protocol (NEXTFLEX Small RNA-seq Kit v3 for Illumina Platforms).
2021-10-18 | E-MTAB-10438 | biostudies-arrayexpress
Project description:The preimplantation development in eutherian mammals is diverse. However, ethical and technical constraints significantly limit our understanding of the molecular and biochemical pathways governing human development. In this study, we discovered an unexpected, species-specific epigenetic pathway regulated by H2A.J, a largely uncharacterized histone variant in preimplantation development using human Blastoid models, IVF bovine embryos, and in vitro human stem cell models. We discovered that H2A.J is expressed in human and bovine placentas, contrasting with its absence in mice, and that H2A.J is essential for trophoblast expansion and viability in human and bovine. Our findings also revealed that H2A.J is enriched at promoters and introns of genes and interacts with RNA Polymerase I and II and pro-elongation factors, thereby regulating RNA Polymerase elongation and trophoblast maintenance in human embryo development. This study sheds light on a novel chromatin factor crucial for proper development in humans and large mammals, offering insights into the evolution of preimplantation development in eutherians. Our research provides valuable insights into evolutionarily divergent epigenetic mechanisms and biological functions in trophoblast lineage maintenance and transcriptional regulation, laying the groundwork for future investigations into the essential but understudied process of human placentation.
2026-03-25 | GSE262635 | GEO
Project description:The preimplantation development in eutherian mammals is diverse. However, ethical and technical constraints significantly limit our understanding of the molecular and biochemical pathways governing human development. In this study, we discovered an unexpected, species-specific epigenetic pathway regulated by H2A.J, a largely uncharacterized histone variant in preimplantation development using human Blastoid models, IVF bovine embryos, and in vitro human stem cell models. We discovered that H2A.J is expressed in human and bovine placentas, contrasting with its absence in mice, and that H2A.J is essential for trophoblast expansion and viability in human and bovine. Our findings also revealed that H2A.J is enriched at promoters and introns of genes and interacts with RNA Polymerase I and II and pro-elongation factors, thereby regulating RNA Polymerase elongation and trophoblast maintenance in human embryo development. This study sheds light on a novel chromatin factor crucial for proper development in humans and large mammals, offering insights into the evolution of preimplantation development in eutherians. Our research provides valuable insights into evolutionarily divergent epigenetic mechanisms and biological functions in trophoblast lineage maintenance and transcriptional regulation, laying the groundwork for future investigations into the essential but understudied process of human placentation.
2026-03-25 | GSE262630 | GEO
Project description:The preimplantation development in eutherian mammals is diverse. However, ethical and technical constraints significantly limit our understanding of the molecular and biochemical pathways governing human development. In this study, we discovered an unexpected, species-specific epigenetic pathway regulated by H2A.J, a largely uncharacterized histone variant in preimplantation development using human Blastoid models, IVF bovine embryos, and in vitro human stem cell models. We discovered that H2A.J is expressed in human and bovine placentas, contrasting with its absence in mice, and that H2A.J is essential for trophoblast expansion and viability in human and bovine. Our findings also revealed that H2A.J is enriched at promoters and introns of genes and interacts with RNA Polymerase I and II and pro-elongation factors, thereby regulating RNA Polymerase elongation and trophoblast maintenance in human embryo development. This study sheds light on a novel chromatin factor crucial for proper development in humans and large mammals, offering insights into the evolution of preimplantation development in eutherians. Our research provides valuable insights into evolutionarily divergent epigenetic mechanisms and biological functions in trophoblast lineage maintenance and transcriptional regulation, laying the groundwork for future investigations into the essential but understudied process of human placentation.
2026-03-25 | GSE262631 | GEO