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Gata3 acts alongside Cdx2 to promote trophoblast gene expression downstream of Tead4 during mouse development

ABSTRACT: The first lineage decisions during mouse development lead to establishment of embryonic and extraembryonic tissues. The transcription factor Cdx2 plays a central role by repressing pluripotency genes, such as Oct4 and promoting trophoblast fate at the blastocyst stage. Here we show that the transcription factor Gata3 is coexpressed with Cdx2 in the blastocyst and that overexpression of Gata3 in embryonic stem cells is sufficient to induce expression of trophoblast genes. Gata3 expression in the blastocyst does not depend on Cdx2, nor do Gata3 overexpressing cell lines require Cdx2 for expression of a subset of trophoblast genes. In the embryo, expression of Gata3, like Cdx2, depends on Tead4, and expression of both factors becomes restricted to nascent trophoblast by an Oct4-independent mechanism. These observations place Tead4 at the top of a trophoblast hierarchy, with Gata3 and Cdx2 acting downstream to induce expression of common and independent targets in this lineage. This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE12999 | GEO | 2010/02/01

SECONDARY ACCESSION(S): PRJNA112611

REPOSITORIES: GEO

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Gata3 acts alongside Cdx2 to promote trophoblast gene expression downstream of Tead4 during mouse development

Project description:The first lineage decisions during mouse development lead to establishment of embryonic and extraembryonic tissues. The transcription factor Cdx2 plays a central role by repressing pluripotency genes, such as Oct4 and promoting trophoblast fate at the blastocyst stage. Here we show that the transcription factor Gata3 is coexpressed with Cdx2 in the blastocyst and that overexpression of Gata3 in embryonic stem cells is sufficient to induce expression of trophoblast genes. Gata3 expression in the blastocyst does not depend on Cdx2, nor do Gata3 overexpressing cell lines require Cdx2 for expression of a subset of trophoblast genes. In the embryo, expression of Gata3, like Cdx2, depends on Tead4, and expression of both factors becomes restricted to nascent trophoblast by an Oct4-independent mechanism. These observations place Tead4 at the top of a trophoblast hierarchy, with Gata3 and Cdx2 acting downstream to induce expression of common and independent targets in this lineage. This SuperSeries is composed of the following subset Series: GSE12985: Differentiation time course of trophoblast stem cells GSE12986: Expression of Cdx2 or Gata3 in R1 mouse embryonic stem cells

2010-02-21 | E-GEOD-12999 | biostudies-arrayexpress

The Role and Mechanism of TEAD4 in Preimplantation Embryonic Development in Mice and Cattle

Project description:Tead4 is a critical transcription factor expressed during preimplantation development and is essential for the expression of trophectoderm-specific genes in mice. However, the mechanism of Tead4’s function in mouse preimplantation development and its conservation across mammals remains unclear. Here, we report that Tead4 is a crucial transcription factor necessary for blastocyst formation in mice. Disruption of TEAD4 through base editing results in developmental arrest at the morula stage. Additionally, RNA-seq analysis reveals dysregulation of 670 genes in Tead4 knockout embryos. As anticipated, Tead4 knockout leads to a decrease in trophectoderm genes CDX2 and GATA3. Intriguingly, we observed a reduction in KRT8, suggesting that Tead4 influences the integrity of the trophectoderm epithelium in mice. More importantly, we noted a decrease in nuclear YAP for Tead4-deficient embryos, indicating that Tead4 directly regulates Hippo signaling. In contrast, bovine embryos with TEAD4 depletion can still develop to blastocysts with normal expression of CDX2, GATA3, and SOX2, albeit with a decrease in total cell number and ICM cell number. In conclusion, we propose that Tead4 regulates mouse blastocyst formation via Krt8 and Yap, both of which are critical regulators of mouse preimplantation development.

2024-07-15 | GSE237418 | GEO

Deciphering a distinct regulatory network of TEAD4, CDX2 and GATA3 in humans for trophoblast transition from embryonic stem cells

Project description:In this study, we perform multiple gain- and loss-of-function of TEAD4, CDX2 or GATA3 to study their roles in the trophoblast transition from BMP4-treated human embryonic stem cells (hESCs). Although hESCs with TEAD4 deletion maintain in pluripotency, their potential of trophoblast transition is attenuate. We then performed large-scale transcriptome analysis to explore more information.

2023-03-17 | GSE147224 | GEO

Altered Subcellular Localization of Transcription Factor TEAD4 Regulates First Mammalian Cell Lineage Commitment

Project description:In the preimplantation mouse embryo TEAD4 is critical to establishing the trophectoderm (TE)-specific transcriptional program and segregating TE from the inner cell mass (ICM). However, TEAD4 is expressed both in the TE and the ICM. Thus, differential function of TEAD4 rather than expression itself regulates specification of the first two cell lineages. We used ChIP-seq to define genome-wide TEAD4 target genes and asked how transcription of TEAD4 target genes is specifically maintained in the TE. Our analyses revealed an evolutionarily conserved mechanism, in which lack of nuclear localization of TEAD4 impairs the TE-specific transcriptional program in inner blastomeres, thereby allowing their maturation towards the ICM lineage. Restoration of TEAD4 nuclear localization maintains the TE-specific transcriptional program in the inner blastomeres and prevents segregation of the TE and ICM lineages and blastocyst formation. We propose that altered subcellular localization of TEAD4 in blastomeres dictates first mammalian cell fate specification. ChIPseq profiles of TEAD4, IgG, Input in Mouse trophoblast stem cells using Illumina HiSeq 2000 and Illumina Genome Analyzer IIx

2012-04-18 | E-GEOD-37350 | biostudies-arrayexpress

Inter-chromosomal enhancer-promoter interaction critical for the appropriate level of Tead4 gene expression at the blastocyst stage [RNA-Seq]

Project description:Although Tead4 is well-known to be critical for blastocyst development and trophoblast lineage differentiation, the higher-order chromatin organization around this gene remains poorly understood. We assayed long-range chromosomal interactions on the Tead4 promoter in mouse embryonic stem (ES) cells and trophoblast stem (TS) cells using the circular chromosome conformation capture (4C)-seq technique. We observed frequent overlaps of genomic regions interacting with the Tead4 promoter and open chromatin regions identified by FAIRE-seq in TS cells. By systematic reporter assays using ES and TS cells, we identified five genomic fragments possessing a TS-specific enhancer activity to the Tead4 promoter, consisting of two intra- and three inter-chromosomal loci relative to the Tead4 gene on chromosome 6. We established five mouse lines deleted with one of the five enhancer elements using CRISPR/Cas9 genome editing, and evaluated the effect of each of the enhancer deletions on the Tead4 gene expression at the blastocyst stage. We observed 35-50% decrease of the Tead4 expression in the blastocysts with heterozygous or homozygous deletion of an inter-chromosomally located enhancer on chromosome 19 compared to that in wild-type blastocysts, whereas the other four deletions did not affect the Tead4 expression level. Our results demonstrate that inter-chromosomal enhancer-promoter interaction bears a critical role in assuring the appropriate level of Tead4 gene expression at the trophoblast lineage specification.

2019-10-22 | GSE134991 | GEO

Inter-chromosomal enhancer-promoter interaction critical for the appropriate level of Tead4 gene expression at the blastocyst stage [FAIRE-Seq]

2019-10-22 | GSE109251 | GEO

Inter-chromosomal enhancer-promoter interaction critical for the appropriate level of Tead4 gene expression at the blastocyst stage [ChIP-Seq]

2019-10-22 | GSE109250 | GEO

Inter-chromosomal enhancer-promoter interaction critical for the appropriate level of Tead4 gene expression at the blastocyst stage [4C-Seq]

2019-10-22 | GSE109249 | GEO

Expression of Cdx2 or Gata3 in R1 mouse embryonic stem cells

Project description:To identify whether Cdx2 or Gata3 can activate trophoblast specific gene expression when expressed in R1 ES cells. To assess the dependency of Gata3 activity on Cdx2, Gata3 was also expressed in Cdx2-null ES cells. Keywords: gene expression a fusion construct of either Cdx2 or Gata3 and the tamoxifen responsive estrogen receptor ligand binding domain was expressed in R1 ES cells. Cell were induced with tamoxifen for 6 days to activate the transcription factor and cultured under trophoblast stem cell conditions

2010-02-21 | E-GEOD-12986 | biostudies-arrayexpress

Pluripotency-Independent Induction of Human Trophoblast Stem Cells from Fibroblasts [ATAC-Seq]

Project description:ATAC-seq analysis revealed similarity/dissimilarity in chromatin accessibility between human blastocyst derived trophoblast stem cells (hbdTSCs), human foreskin fibroblasts (HFFs) and pluripotent stem cells (hESCs) compared with HFFs which underwent 3 days of ectopic expression of GATA3, OCT4, KLF4, MYC (GOKM) or OCT4, SOX2, KLF4 and MYC (OSKM).

2023-02-21 | GSE182012 | GEO

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