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CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development [ChIP-seq]

ABSTRACT: CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development [ChIP-seq]

PROVIDER: PRJNA1022003 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26205180.fastq.gz	Fastqsanger.gz
	SRR26205181_1.fastq.gz	Fastqsanger.gz
	SRR26205181_2.fastq.gz	Fastqsanger.gz
	SRR26205182.fastq.gz	Fastqsanger.gz
	SRR26205183_1.fastq.gz	Fastqsanger.gz

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CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development

Project description:CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development

| PRJNA1022000 | ENA

CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development [HiChIP]

Project description:CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development [HiChIP]

| PRJNA1022005 | ENA

CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development [RNA-seq]

Project description:CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development [RNA-seq]

| PRJNA1022008 | ENA

CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development [HiChIP]

Project description:The placenta serves as the interface between the mother and fetus, facilitating the exchange of gases and nutrients between their separate blood circulation systems. Trophoblasts in the placenta play a central role in this process. Our current understanding of mammalian trophoblast development relies largely on mouse models. However, given the diversification of mammalian placentas, findings from the mouse placenta cannot be readily extrapolated to other mammalian species, including humans. To fill this knowledge gap, we performed CRISPR knockout (KO) screening in human trophoblast stem cells (hTSCs). We targeted genes essential for mouse placental development and identified more than 100 genes as critical regulators in both human hTSCs and mouse placentas. Among them, we further characterized in detail two transcription factors, DLX3 and GCM1, and revealed their essential roles in hTSC differentiation. Moreover, a gene function-based comparison between human and mouse trophoblast subtypes suggests that their relationship may differ significantly from previous assumptions based on tissue localization or cellular function. Notably, our data reveal that hTSCs may not be analogous to mouse TSCs or the extraembryonic ectoderm (ExE) in which in vivo TSCs reside. Instead, hTSCs may be analogous to progenitor cells in the mouse ectoplacental cone and chorion. This finding is consistent with the absence of ExE-like structures during human placental development. Our data not only deepen our understanding of human trophoblast development but also facilitate cross-species comparison of mammalian placentas.

2023-11-09 | GSE244253 | GEO

CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development [ChIP-seq]

2023-11-09 | GSE244252 | GEO

CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development [RNA-seq]

2023-11-09 | GSE244254 | GEO

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

Matrix directs trophoblast differentiation in a bioprinted organoid model of early placental development

Project description:Trophoblast organoids offer a unique opportunity to study mechanisms orchestrating placental growth and development during pregnancy. However, many organoid cultures rely on extracellular matrix reagents that are highly variable and unable to be tuned to reflect in vivo tissues. Here we describe the first bioprinted placental organoid model, generated using first trimester trophoblast cell line, ACH-3P, and a synthetic polyethylene glycol matrix. Bioprinted organoids were compared comprehensively to classic Matrigel-embedding using functional assays, immunofluorescence microscopy, transcriptomic and proteomic analyses. Organoids differentiated spontaneously from cytotrophoblasts into two major subtypes: extravillous trophoblasts (EVTs) and syncytiotrophoblasts (STBs), with bioprinted organoids driven towards EVT differentiation. Bioprinted organoids were exposed to inflammation and treated with aspirin or metformin to assess their effects on trophoblast organoid formation and viability. Further, we reversed the inside-out architecture of ACH-3P organoids by suspension culture. Organoid suspension caused STBs to form a syndecan-1+ outer layer on the periphery of organoids, reflecting placental tissue. Here, we present an alternative trophoblast organoid model with further tuning potential to reflect the placental microenvironment in physiological and pathological pregnancies.

2025-07-28 | PXD056796 | Pride

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.

2023-08-03 | GSE229702 | 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 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

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