Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA357115 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5099923.fastq.gz | Fastqsanger.gz | |||
| SRR5099924.fastq.gz | Fastqsanger.gz |
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Project description:Genetic Redundancy of GATA Factors in Extraembryonic Trophoblast Lineage Ensures Progression of both Pre and Postimplantation Mammalian Development
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Project description:GATA transcription factors are implicated in establishing cell fate during mammalian development. In early mammalian embryos, GATA3 is selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast fate. However, trophoblast-specific GATA3 function is dispensable for early mammalian development. Here, using dual conditional knockout mice, we show that genetic redundancy of GATA3 with paralog GATA2 in trophoblast progenitors ensures the successful progression of both pre and postimplantation mammalian development. Stage-specific gene deletion in trophoblasts reveals that loss of both GATA genes, but not either one alone, leads to embryonic lethality prior to the onset of their expression within the embryo proper. Using ChIP-seq and RNA-seq analyses, we define the global targets of GATA2/GATA3 and show that they directly regulate a large number of common genes to orchestrate stem vs. differentiated trophoblast fate. Also, in trophoblast progenitors GATA factors directly regulate BMP4, Nodal and Wnt signaling components that promote embryonic-extraembryonic signaling cross-talk, essential for the development of the embryo proper. Our study provides genetic evidence that impairment of trophoblast-specific GATA2/GATA3 function could lead to early pregnancy failure.
2017-01-25 | GSE92292 | GEO
Project description:GATA transcription factors are implicated in establishing cell fate during mammalian development. In early mammalian embryos, GATA3 is selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast fate. However, trophoblast-specific GATA3 function is dispensable for early mammalian development. Here, using dual conditional knockout mice, we show that genetic redundancy of GATA3 with paralog GATA2 in trophoblast progenitors ensures the successful progression of both pre and postimplantation mammalian development. Stage-specific gene deletion in trophoblasts reveals that loss of both GATA genes, but not either one alone, leads to embryonic lethality prior to the onset of their expression within the embryo proper. Using ChIP-seq and RNA-seq analyses, we define the global targets of GATA2/GATA3 and show that they directly regulate a large number of common genes to orchestrate stem vs. differentiated trophoblast fate. Also, in trophoblast progenitors GATA factors directly regulate BMP4, Nodal and Wnt signaling components that promote embryonic-extraembryonic signaling cross-talk, essential for the development of the embryo proper. Our study provides genetic evidence that impairment of trophoblast-specific GATA2/GATA3 function could lead to early pregnancy failure.
2017-01-25 | GSE92287 | GEO
Project description:Genetic Redundancy of GATA Factors in Extraembryonic Trophoblast Lineage Ensures Progression of both Pre and Postimplantation Mammalian Development [ChIP-seq]
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Project description:GATA transcription factors, particularly GATA2 and GATA3 are selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast self-renewal during mammalian development. However, we have a poor understanding about the contribution of these GATA factors, in the process of syncytiotrophoblast (SynT) development. Thus, the goal of this study is to define the importance of GATA2 and GATA3 in orchestrating a global gene expression program that poises and commits mammalian trophoblast stem cells to the SynT lineage. Using the cut and run technique for GATA2 and GATA3 antibodies in the human trophoblast stem cells we are aiming to identify the direct targets of the GATA transcription factors that are essential for determining the SynT lineage. Three individual experiments were performed.
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Project description:We derive experimental conditions for the derivation of marmoset trophoblast like cells. Marmoset naïve PSC form extraembryonic mesoderm in human TSC conditions, whilst TGFβ/NODAL, FGF/ERK and WNT signalling control marmoset peri- and postimplantation trophoblast identity.
2024-11-21 | E-MTAB-12463 | biostudies-arrayexpress
Project description:During mammalian preimplantation development, lineage specification is accompanied by dynamic epigenetic remodeling following zygotic genome activation. In particular, repressive histone modifications display lineage-specific distributions, suggesting a role in constraining cell fate potential. While Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 has been implicated in restricting extraembryonic lineage programs in embryonic stem cells (ESCs), whether additional chromatin mechanisms cooperate to reinforce this barrier remains unclear. Here, we show that dual inhibition of H3K27me3 and H3K9me2/3 markedly increases extraembryonic plasticity in ESCs by relieving repressive chromatin constraints at lineage-specific gene sets. ESCs under defined conditions with reduced H3K27me3 and H3K9me2/3 exhibit a distinct intermediate cell state with both trophoblast (TE)- and primitive endoderm (PrE)-like features. These cells form blastoids together with naïve ESCs, induce decidua formation, and contribute to the placenta in vivo following morula aggregation, demonstrating functional extraembryonic competence. Collectively, our findings identify H3K27me3 and H3K9me3 as key repressive histone methylation marks that cooperatively act as a chromatin barrier restricting extraembryonic lineage potential in pluripotent stem cells, thereby safeguarding pluripotent identity.
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Project description:Placental development is a key event in mammalian reproduction and embryogenesis. However, the molecular basis underlying extraembryonic lineage specification and subsequent placental development is not fully understood. Through a genetic screen, we identified Zfp281 as a key factor for extraembryonic development. Disruption of Zfp281 in mice caused severe defects in extraembryonic as well as embryonic tissues. Importantly, Zfp281 was preferentially expressed in the trophoblast stem cell population in an FGF-dependent manner and ensured the expression of genes necessary for placental development. Through the analysis of transcriptome and epigenome, we identified Zfp281 as an important factor to shape the transcriptome of mammalian trophoblast stem cells.
2019-05-07 | GSE111824 | GEO
Project description:The mammalian blastocyst consists of three distinct cell types: epiblast, trophoblast (TB), and primitive endoderm (PrE). Although embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) retain the functional properties of Epi and TB, the currently available extraembryonic endoderm cells (XENC) do not fully recapitulate the developmental potential of PrE. Here we report derivation of primitive endoderm stem cells (PrESCs) in mice. PrESCs express both PrE and pluripotency marker genes like founder PrE. These cells are efficiently incorporated into PrE upon blastocyst injection, generate functionally competent PrE-derived tissues, and support fetal development of PrE-depleted blastocysts in chimeras. Establishment of PrESCs therefore represents a significant step-forward in elucidating the mechanisms for PrE specification and subsequent pre- and post-implantation development.
2021-12-31 | GSE185461 | GEO
Project description:The placenta establishes a maternal–fetal exchange interface which ensures transportation of nutrients and gases between the mother and the fetus. A critically conserved step in the establishment of this exchange surface in mammals is the fusion of trophoblast cells into a multinucleated syncytiotrophoblasts (SynT). In mice, SynTs develop via differentiation of the labyrinth trophoblast progenitors (LaTP) of the developing placenta, and in humans, SynTs develop via differentiation of villous cytotrophoblast (CTB) progenitors. Despite being an indispensable step for mammalian development in utero, conserved molecular mechanisms that ensure SynT development are poorly understood. Herein, we show that GATA2 and GATA3 (GATA factors) plays an essential role in labyrinth trophoblast progenitors (LaTPs) thereby committing these cells towards the SynT differentiation program. Mature syncytial layer specific immunostaining with established markers, and ultrastructure analysis of the labyrinth revealed that the loss of GATA factors was impairing the formation of mature SynT cells. We therefore focused our attention on the status of the labyrinth progenitor trophoblast cells in the GATA DKO vs the control placentae. To do that we performed single cell RNA Sequencing (scRNA-Seq) with E9.5 control and Gcm1Cre GATA KO placentae.
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