Deciphering a distinct regulatory network of TEAD4, CDX2 and GATA3 in humans for trophoblast transition from embryonic stem cells
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PROVIDER: PRJNA613450 | ENA |
REPOSITORIES: ENA
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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
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
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 SubSeries listed below.
2010-02-01 | GSE12999 | GEO
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
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
2010-02-01 | GSE12986 | GEO
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
Project description:Current understandings of the initiation of the trophectoderm (TE) program in mammalian embryonic development lacks evidence of how TE-associated factors such as CDX2 and GATA3 participate in bovine lineage specification. In this study, we describe the effects of TE-associated factors on lineage specification marker genes such as SOX2, OCT4, NANOG, GATA6 and SOX17, assisted by a cytosine base editor system. Interestingly, GATA3 downregulates the NANOG expression in bovine blastocysts. Further analysis of the blastocyst mosaic shows that GATA3 is required for NANOG in TE cells of bovine blastocysts. It is worthy to notice that, unlike mouse embryos where GATA3 and CDX2 did not reciprocally affect each other in bovine embryos.
2022-10-26 | GSE216123 | GEO
Project description:In order to study early developmental events in the mammalian embryo it is often desirable to be able to impair expression of specific genes. While DNA and RNA methods are routine, protein methods are still at the very beginning. When a specific antibody is supplied to mouse oocytes expressing the ubiquitin-protein ligase TRIM21, a ternary complex forms with the target protein, leading to its rapid and acute degradation - hence the name 'Trim-away' (PMID 29153837). However, there are many unknowns in this new endeavour. First and foremost, the extent to which endogenous proteins can be depleted depends on their amount, in relation to the amount of exogenous antibody, which is limited by the microinjection procedure. Secondly, the depletion of the protein must be sustained over days. Using the iBAQ algorithm we show that proteins found in preimplantation mouse embryos range from 3,5E-10 to 2,6E-02 picomoles. These amounts are tractable with our microinjection method, which supplies up to 100 picoliters and up to 6,7E-4 picomoles antibody before incurring in toxic effects on mouse development. Building on these data, we demonstrate the feasibility of protein knock-down for a gene which is essential in the preimplantation mouse embryo, namely TEAD4 (TEA domain family member 4). Protein knock-down persists for sufficient time to result in a phenotype which is entirely consistent with that of the null mutation (Tead4 -/-) and of the RNA interference, namely: significantly reduced mRNA expression of TEAD4 target genes Cdx2 and Gata3, and embryo’s inability to implant. We conclude that for a time window of 3-4 days of preimplantation development the protein depletion method can be a valid alternative to DNA and RNA methods. After in vivo fertilization and short culture in KSOM(aa) medium, pronuclear-stage oocytes (B6C3F1 x CD1) were microinjected with Trim21 mRNA and dextran beads as tracer (named 'group 4'), or Trim21 mRNA, dextran beads and anti-GFP antibody (named 'group 5'), or Trim21 mRNA, dextran beads and anti-TEAD4 antibody (named 'group 6'), two replicates each ('a' and 'b'). On day 4 after microinjection, the most advanced embryos were examined for phenotype or lysed for transcriptome analysis. TEAD4-depleted embryos formed only 30% blastocysts and these were not able to implant in the outgrowth assay, in contrast to the almost full rates of the embryos injected with Trim21 mRNA or Trim21 mRNA + anti-GFP antibody. Transcriptome analysis revealed that the TEAD4 target genes Cdx2 and Gata3 are significantly reduced in the embryos that received the anti-TEAD4 antibody compared to the embryos that received Trim21 mRNA only, while the embryos that received anti-GFP antibody were much similar to those that received Trim21 mRNA only.
2019-07-10 | GSE124844 | GEO
Project description:Functional role of GATA3 and CDX2 in lineage specification during bovine early embryonic development
| PRJNA892118 | ENA