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Stem cell-derived trophoblast organoids model human placental development and susceptibility to emerging pathogens

ABSTRACT: Stem cell-derived trophoblast organoids model human placental development and susceptibility to emerging pathogens

PROVIDER: PRJNA722510 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14255152_1.fastq.gz	Fastqsanger.gz
	SRR14255152_2.fastq.gz	Fastqsanger.gz
	SRR14255153_1.fastq.gz	Fastqsanger.gz
	SRR14255153_2.fastq.gz	Fastqsanger.gz
	SRR18932993_1.fastq.gz	Fastqsanger.gz

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Stem cell-derived trophoblast organoids model human placental development and susceptibility to emerging pathogens

Project description:Trophoblast organoids derived from placental villi provide a 3D model system of human placental development, but access to first-trimester tissues is limited. Here we report that trophoblast stem cells isolated from naïve human pluripotent stem cells (hPSCs) can efficiently self-organize into 3D stem cell-derived trophoblast organoids (SC-TOs) with a villous architecture similar to primary trophoblast organoids. Single cell transcriptome analysis reveals the presence of distinct cytotrophoblast and syncytiotrophoblast clusters and a small cluster of extravillous trophoblasts, which closely correspond to trophoblast identities in the post-implantation embryo. These organoid cultures display clonal X chromosome inactivation patterns previously described in the human placenta. We further demonstrate that SC-TOs exhibit selective vulnerability to emerging pathogens (SARS-CoV-2 and Zika virus), which correlates with expression levels of their respective entry factors. The generation of trophoblast organoids from naïve hPSCs provides an accessible 3D model system of the developing placenta and its susceptibility to emerging pathogens.

2022-04-29 | GSE172241 | GEO

Stem-cell-derived trophoblast organoids model human placental development and susceptibility to emerging pathogens.

Project description:Trophoblast organoids derived from placental villi provide a 3D model system of human placental development, but access to first-trimester tissues is limited. Here, we report that trophoblast stem cells isolated from naive human pluripotent stem cells (hPSCs) can efficiently self-organize into 3D stem-cell-derived trophoblast organoids (SC-TOs) with a villous architecture similar to primary trophoblast organoids. Single-cell transcriptome analysis reveals the presence of distinct cytotrophoblast and syncytiotrophoblast clusters and a small cluster of extravillous trophoblasts, which closely correspond to trophoblast identities in the post-implantation embryo. These organoid cultures display clonal X chromosome inactivation patterns previously described in the human placenta. We further demonstrate that SC-TOs exhibit selective vulnerability to emerging pathogens (SARS-CoV-2 and Zika virus), which correlates with expression levels of their respective entry factors. The generation of trophoblast organoids from naive hPSCs provides an accessible 3D model system of the developing placenta and its susceptibility to emerging pathogens.

| S-EPMC9136997 | biostudies-literature

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

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.

2018-11-28 | E-MTAB-6683 | biostudies-arrayexpress

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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HCA Placental Infection Atlas

Project description:HCA Placental Infection Atlas Self-renewing human trophoblast stem cells (hTSC) can give rise to major trophoblast lineages, including syncytiotrophoblast (SCT) and extravillous trophoblast (EVT). hTSC has facilitated the study of placental development and function in vitro. Here, we aim to utilise the hTSC line (HMDMC 20/0005) to study human placental infection and inflammation. This study will provide the opportunity to better understand the pathogenesis of human placenta in the event of infection and inflammation. In brief, differentiated hTSC will be infected with relevant pathogens and stimulated with a panel of inflammatory cytokines. We will use single-cell genomic and spatial approaches to characterise cellular heterogeneity in response to infection or cytokines stimulus. In parallel, we will investigate the interaction between iPSC-derived macrophages with different trophoblast lineages during the course of infection using single-cell genomic and spatial methods. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

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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

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.

2015-12-01 | GSE65808 | GEO

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

2015-12-01 | GSE65807 | GEO

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

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

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