The Trophoblast Compartment Helps Maintain Embryonic Pluripotency and Delays Differentiation towards Cardiomyocytes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA988165 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25046137_1.fastq.gz | Fastqsanger.gz | |||
| SRR25046137_2.fastq.gz | Fastqsanger.gz | |||
| SRR25046138_1.fastq.gz | Fastqsanger.gz | |||
| SRR25046138_2.fastq.gz | Fastqsanger.gz | |||
| SRR25046139_1.fastq.gz | Fastqsanger.gz |
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Project description:Normal developmental progression relies on a close crosstalk between the embryonic and extraembryonic lineages in the pre- and peri-gastrulation conceptus. This has been demonstrated in the mouse where epiblast-derived FGF and NODAL signals are required to maintain a stem-like state in trophoblast cells of the extraembryonic ectoderm, while visceral endoderm signals are pivotal to pattern the anterior region of the epiblast. These developmental stages also coincide with the specification of the first heart precursors. Here, we established a robust differentiation protocol of mouse embryonic stem cells (ESCs) into cardiomyocytes that we used to test the impact of trophoblast on this key developmental process. Using trophoblast stem cells (TSCs) to produce trophoblast-conditioned medium (TCM), we show that TCM profoundly slows down the cardiomyocyte differentiation dynamics and specifically delays the emergence of cardiac mesoderm progenitors. TCM also strongly promotes the retention of pluripotency transcription factors. By applying TCM from various mutant TSCs, we further show that specifically those mutations that cause a trophoblast-mediated effect on early heart development alter the normal cardiomyocyte differentiation trajectory. Our approaches provide a meaningful deconstruction of the intricate crosstalk between the embryonic and the extraembryonic compartments. They demonstrate that trophoblast helps prolong a pluripotent state in embryonic cells by delaying early differentiative processes, likely through secretion of leukemia inhibitory factor (LIF). These data expand our knowledge of the multifaceted signalling interactions between distinct compartments of the early conceptus that ensure normal embryogenesis, insights that will also be of great importance for the field of synthetic embryo research.
2023-08-09 | GSE236001 | GEO
Project description:Normal developmental progression relies on close interactions between the embryonic and extraembryonic lineages in the pre- and peri-gastrulation stage conceptus. For example, mouse epiblast-derived FGF and NODAL signals are required to maintain a stem-like state in trophoblast cells of the extraembryonic ectoderm, while visceral endoderm signals are pivotal to pattern the anterior region of the epiblast. These developmental stages also coincide with the specification of the first heart precursors. Here, we established a robust differentiation protocol of mouse embryonic stem cells (ESCs) into cardiomyocyte-containing embryoid bodies that we used to test the impact of trophoblast on this key developmental process. Using trophoblast stem cells (TSCs) to produce trophoblast-conditioned medium (TCM), we show that TCM profoundly slows down the cardiomyocyte differentiation dynamics and specifically delays the emergence of cardiac mesoderm progenitors. TCM also strongly promotes the retention of pluripotency transcription factors, thereby sustaining the stem cell state of ESCs. By applying TCM from various mutant TSCs, we further show that those mutations that cause a trophoblast-mediated effect on early heart development in vivo alter the normal cardiomyocyte differentiation trajectory. Our approaches provide a meaningful deconstruction of the intricate crosstalk between the embryonic and the extraembryonic compartments. They demonstrate that trophoblast helps prolong a pluripotent state in embryonic cells and delays early differentiative processes, likely through production of leukemia inhibitory factor (LIF). These data expand our knowledge of the multifaceted signaling interactions among distinct compartments of the early conceptus that ensure normal embryogenesis, insights that will be of significance for the field of synthetic embryo research.
| S-EPMC10418709 | biostudies-literature
Project description:In the bovine placenta, intimate fetomaternal contacts are confined to multiple discrete structures termed placentomes. In the placentomes, widely ramified fetal chorionic villi interdigitate with corresponding maternal caruncular crypts. The trophoblast covering the chorionic villi is composed of uninucleate trophoblast cells (UTCs) and binucleate trophoblast giant cells (TGCs). TGCs are weakly invasive and capable of migrating toward the caruncular epithelium where they eventually fuse with single epithelial cells to form short-living trinucleate fetomaternal hybrid cells. Thereby, molecules of fetal origin are transported into the maternal compartment. The loss of TGCs due to fetomaternal hybrid cell formation is compensated by differentiation of UTCs into TGCs. We performed a genome-wide gene expression study of virtually pure UTCs and TGCs to to identify genes which are associated with trophoblast cell differentiation
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Project description:Elf5 is a transcription factor with pivotal roles in the trophoblast compartment where it reinforces a trophoblast stem cell (TSC)-specific transcriptional circuit. However, Elf5 is also present in differentiating trophoblast cells that have ceased to express other TSC genes such as Cdx2 and Eomes. In the current study we aimed to elucidate the context-dependent role of Elf5 at the interface between TSC self-renewal and onset of differentiation. We demonstrate that precise levels of Elf5 are critical for normal expansion of the TSC compartment and embryonic survival, as Elf5 overexpression triggers precocious trophoblast differentiation. Through integration of protein interactome, transcriptome and genome-wide chromatin immunoprecipitation data we reveal that this abundance-dependent function is mediated through a shift in preferred Elf5 binding partners; in TSCs, Elf5 interaction with Eomes recruits Tfap2c to triply occupied sites at TSC-specific genes driving their expression. By contrast, the Elf5 and Tfap2c interaction becomes predominant as their protein levels increase. This triggers binding to double and single occupancy sites that harbour the cognate Tfap2c motif, causing activation of the associated differentiation-promoting genes. These data place Elf5 at the centre of a stoichiometry-sensitive transcriptional network where it acts as molecular switch governing the balance between TSC proliferation and differentiation.
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Project description:Human embryonic stem cells (hESC) can be differentiated towards progeny resembling trophoblast upon exposure to BMP4. Here we analysed transcriptional changes in cells undergoing commitment to trophoblast at 6 time points using total RNA sequencing and identified early and late regulators of trophoblast fate.
2017-10-14 | GSE104969 | GEO
Project description:Infection with SARS-CoV-2 in pregnancy has been associated with poor maternal and neonatal outcomes and placental defects. The placenta, which acts as a physical and immunological barrier at the maternal/fetal interface, is not established until the end of the first trimester. Therefore, localized viral infection of the trophoblast compartment early in gestation could trigger an inflammatory response resulting in altered placental function and consequent suboptimal conditions for fetal growth and development. In this study, we investigated the effect of SARS-CoV-2 infection in early gestation placentae using placenta-derived human trophoblast stem cells (TSC), a novel in vitro model, and their extra-villous trophoblast (EVT) and syncytiotrophoblast (STB) derivatives. Consistent with host viral entry protein expression, SARS-CoV-2 was able to productively replicate in TSC-derived STB and EVT but not undifferentiated TSC. Both early EVT and STB elicited an interferon-mediated innate immune response similar to other cells infected with this virus. Therefore, we have also shown that placenta derived TSCs are a robust in vitro model to investigate the effect of this viral infection in the trophoblast compartment of the early placenta. Overall, these results suggest that SARS-CoV-2 infection in early gestation can adversely affect placental development and that might occur via directly infecting the differentiated trophoblast compartment, thus posing a higher risk for poor pregnancy outcomes.
2023-10-14 | GSE216484 | GEO
Project description:Trophectoderm-specific expression of Angiomotin (AMOT) in pre-implantation embryos followed by its unique expression in the post-implantation ectoplacental cone that harbors the trophoblast stem cell niche prompted our investigation on the function of AMOT in trophoblast cells. Using the in vitro trophoblast stem cell culture model, we established differentiation dependent up-regulation of AMOT expression in trophoblast cells. To understand the function of AMOT in trophoblast cells mass spectrometry-based proteomic analysis was employed to identify the AMOT interactome within the trophoblast proteome. This approach utilized immunoprecipitation of endogenous AMOT followed by fractionation on SDS-PAGE and subsequently subjecting the tryptic digested excised gel bands to mass spectrometry.
2021-11-03 | PXD019391 | Pride
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.
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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.
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