Ontology highlight
ABSTRACT:
PROVIDER: PRJNA872824 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21185813_1.fastq.gz | Fastqsanger.gz | |||
| SRR21185813_2.fastq.gz | Fastqsanger.gz | |||
| SRR21185814_1.fastq.gz | Fastqsanger.gz | |||
| SRR21185814_2.fastq.gz | Fastqsanger.gz | |||
| SRR21185815_1.fastq.gz | Fastqsanger.gz |
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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:This dataset is part of a study that aims to compare in vivo human trophoblast differentiation into EVTs to different in vitro trophoblast organoids using single-cell and single-nuclei RNA sequencing. This specific dataset includes scRNA-seq and snRNA-seq data from 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) together with EVT differentiation media. 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. Data for primary trophoblast organoids is available under E-MTAB-12650.
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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.
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Project description:To understand the human placenta development, we investigated the features of two trophoblast models, trophoblast organoids and trophoblast stem cells, with the aim of identifying which type of trophoblast in vivo they most closely resemble. To this end, we profiled the transcriptomes from the two models by using the Truseq stranded mRNA library kit (Illumina).
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Project description:To understand the human placenta development, we investigated the features of two trophoblast models, trophoblast organoids and trophoblast stem cells, with the aim of identifying which type of trophoblast in vivo they most closely resemble. To this end, we profiled the microRNAs from the two models by using the Bioo Nextflex protocol (NEXTFLEX Small RNA-seq Kit v3 for Illumina Platforms).
2021-10-18 | E-MTAB-10438 | biostudies-arrayexpress
Project description:CCR7 chemokine G protein-coupled receptor is expressed in extraembryonic tissues of the early human embryo, including trophectoderm and its derivatives cytotrophoblast (CTB), extravillous trophoblast (EVT), and syncytiotrophoblast (STB). However, its function in placental development remains poorly explored. Here, we generated human embryonic stem cells harboring CCR7 deletions and differentiated them into human trophoblast stem cell (hTSC) and hTSC-derived trophoblast organoids. We found that CCR7 mutant EVTs retained hTSC-like characteristics, exhibited decreased epithelial-to-mesenchymal transition, and reduced cell motility. Additionally, CCL21-CCR7 induced EVT terminal differentiation into endovascular EVT-like cells. Transcriptional profiling in CCR7 KO STBs identified reduced viral defense gene expression related to the protection against maternal-fetal transmission. Investigation of trophoblast organoids using single cell transcriptome profiling showed that CCR7 mutant trophoblast organoids comprised a smaller EVT population, but a larger STB population, compared to wild type organoids, while CellChat analysis indicated altered cell-cell communication including WNT, ACTIVIN, and IFN-I signaling pathways. Mechanistically, we found that CCR7 limited the cell-cell fusion of early STB differentiation by reducing cAMP levels. Together, our studies demonstrate that CCR7 plays multiple roles in cellular decision-making during trophoblast differentiation, promoting EVT differentiation, and limiting cell-cell fusion during early STB differentiation.
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Project description:CCR7 chemokine G protein-coupled receptor is expressed in extraembryonic tissues of the early human embryo, including trophectoderm and its derivatives cytotrophoblast (CTB), extravillous trophoblast (EVT), and syncytiotrophoblast (STB). However, its function in placental development remains poorly explored. Here, we generated human embryonic stem cells harboring CCR7 deletions and differentiated them into human trophoblast stem cell (hTSC) and hTSC-derived trophoblast organoids. We found that CCR7 mutant EVTs retained hTSC-like characteristics, exhibited decreased epithelial-to-mesenchymal transition, and reduced cell motility. Additionally, CCL21-CCR7 induced EVT terminal differentiation into endovascular EVT-like cells. Transcriptional profiling in CCR7 KO STBs identified reduced viral defense gene expression related to the protection against maternal-fetal transmission. Investigation of trophoblast organoids using single cell transcriptome profiling showed that CCR7 mutant trophoblast organoids comprised a smaller EVT population, but a larger STB population, compared to wild type organoids, while CellChat analysis indicated altered cell-cell communication including WNT, ACTIVIN, and IFN-I signaling pathways. Mechanistically, we found that CCR7 limited the cell-cell fusion of early STB differentiation by reducing cAMP levels. Together, our studies demonstrate that CCR7 plays multiple roles in cellular decision-making during trophoblast differentiation, promoting EVT differentiation, and limiting cell-cell fusion during early STB differentiation.
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Project description:Human trophoblast organoid serves as a revolutionary tool for studying trophoblast cell development and maternal-fetal interactions. However, currently reported trophoblast organoids exhibited opposite trophoblast polarity to in vivo or a solid cell spheroid lacking of central villous core-like cavity, both of which fail to model the physiological structure of in vivo placenta villi. Here, using human naïve embryonic stem cells, we constructed a trophoblast organoid with both peripheral apical-out bilaminar trophoblast cells and central villous core-like cavity, named ppTO. Besides, ppTO simulated the typical molecular and secretory features of in vivo trophoblast. Single-cell RNA sequencing (scRNA-seq) analysis demonstrated that the development of ppTO simulated in vivo trophoblast syncytialization process and pan-trophoblast transcriptome features. Using ppTO, we revealed that the syncytialization process relied on a suppressed HIPPO signaling for initiating syncytialization and followed by a reactivated HIPPO signaling for STB maturation. By comparative study with reported organoids, we revealed the important role of the expression and orientation of polarity molecule aPKC in the formation and spatial patterning of STB within trophoblast organoids. In summary, we develop a trophoblast organoid simulating the physiological structure and molecular features of placental villous trophoblast for studying the mechanisms underlying trophoblast development and function.
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Project description:The establishment and function of the human placenta is dependent on specialized cells called trophoblasts. Unfortunately, little is known about the cellular and molecular processes controlling human trophoblast stem cell maintenance and differentiation into mature trophoblast sub-populations/cell states. To address this, we here report transcriptomic data from n=7 first trimester human placental tissues, n=3 regenerative human trophoblast stem cell (hTSC) derived trophoblast organoids, and n=3 EVT-differentiated hTSC derived organoid cultures at single-cell resolution. This study sought to identify the molecular programs and cell states important in trophoblast progenitor establishment, renewal, and differentiation. Placental tissues were collected following elective termination at the British Columbia Women’s Hospital CARE clinic. hTSC cultures were established as described and sequenced on either day 0 of culture (for regenerative organoid colonies), or day 7 of culture (for EVT-differentiated organoid colonies).
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