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Zfp281 shapes the transcriptome of trophoblast stem cells and is essential for placental development

ABSTRACT: Zfp281 shapes the transcriptome of trophoblast stem cells and is essential for placental development

PROVIDER: PRJNA438284 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6833730.fastq.gz	Fastqsanger.gz
	SRR6833731.fastq.gz	Fastqsanger.gz
	SRR6833732.fastq.gz	Fastqsanger.gz
	SRR6833723.fastq.gz	Fastqsanger.gz
	SRR6833733.fastq.gz	Fastqsanger.gz

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Zfp281 shapes the transcriptome of trophoblast stem cells and is essential for placental development

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

Transcription profiling of placental trophoblast stem cells time dependent response to hyperosmolar stress

Project description:Stress induces undifferentiated stem cells to differentiate in a way that looks like normal differentiation; We used hyperosmolar stress as a generic, energy-depleting stressor and tested for the global changes in the transcriptional response of placental trophoblast stem cells Experiment Overall Design: Placental trophoblast stem cells were subjected to 0, 0.5, 2, 6, and 24 hours of hyperosmolar stress and then assayed by Affymetrix 430MOE V2 whole mouse genome arrays.

2008-11-13 | E-GEOD-9519 | biostudies-arrayexpress

Combining ChIP-Seq and RNA-Seq data in early placental development to study trophoblast invasion [RNA-Seq]

Project description:The placenta is an understudied organ that has a critical role in mammalian development. In early placental development, the essential process of trophoblast invasion establishes adequate blood flow between mother and fetus. Despite its importance, little is known about the genomic regions responsible for regulating trophoblast invasion. In order to identify enhancers that are important for regulating the process, we carried out ChIP-Seq for an enhancer-associated mark at two time points during early placental development. Combining these data with RNA-Seq data and protein interaction data allowed us to construct a gene-enhancer network describing trophoblast invasion.

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Transcriptomic profile of human placenta derived trophoblast organoid cultures with its tissue of origin, human placental villi.

Project description:The aim of this microarray experiment was to compare the overall transcriptomic profile of human placenta derived trophoblast organoid cultures with its tissue of origin, human placental villi. As the placental villi contains both trophoblast and stromal populations, we have included placenta derived stromal cultures in this comparison.

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Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [RNA-seq]

Project description:The placental DNA methylation landscape is unique, with widespread partially methylated domains (PMDs) and hundreds of placental-specific imprinted domains. Furthermore, the placental ‘methylome’ has been the focus of extensive study for links with pregnancy complications. Human trophoblast stem cells (hTSCs) offer exciting potential for functional epigenetic studies; however, whether the hTSC epigenome recapitulates primary cytotrophoblast, remains poorly described. In this study, we demonstrate that hTSCs exhibit an atypical methylome, with DNA methylation present over transcribed gene bodies but a complete loss of placental PMDs. Using single-cell RNA-seq from human embryogenesis, hTSCs display a notable absence of DNMT3L expression. Ectopic expression of DNMT3L in hTSCs restored placental PMDs. DNMT3L-expressing hTSCs showed comparable stemness but failed to syncytialise in organoid culture, associated with hypermethylation of STB transcription factor motifs. These findings reveal that DNMT3L is essential in establishing the human placental methylome and that DNMT3L downregulation is necessary for successful trophoblast differentiation.

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Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [ChIP-seq]

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Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [PBAT BS-Seq]

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Gpr126 is essential for placental development

Project description:Gpr126 is essential for placental development

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Zika virus targets human trophoblast stem cells and prevents syncytialization in placental trophoblast organoids

Project description:Zika virus (ZIKV) infection during pregnancy results in an increased risk of spontaneous abortion and vertical transmission across placenta results in severe congenital defects in newborns. While the infectivity and pathological effects of ZIKV on the placental trophoblast progenitor cells in early human embryos remains largely unknown. Here, using the human trophoblast stem cells (hTSCs) isolated from human blastocyst, we showed that hTSCs were permissive to ZIKV infection, while resistance to ZIKV increased with differentiation. Combined CRISPR/Cas9-mediated gene knockout and RNA-seq assays, we demonstrated that the intrinsic expression of AXL and TIM-1, as well as the absence of potent interferon (IFN)-stimulated genes (ISGs), contributed to the high sensitivity of hTSCs to ZIKV. Furthermore, using our newly developed hTSC-derived 3 dimensional (3D) placental trophoblast organoid model, we demonstrated that ZIKV infection completely disrupted the structure of mature hTSC-organoids and inhibited syncytialization. Overall, our results clearly demonstrated that hTSCs represented the major target cells of ZIKV, and a possible reduced syncytialization may result from ZIKV infection of early developing placenta. These findings deepened our understanding of the characteristics and consequences of ZIKV infection of trophoblast stem cells in early human embryo.

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