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Regionally distinct trophoblast regulate barrier function and invasion in the human placenta

ABSTRACT: Regionally distinct trophoblast regulate barrier function and invasion in the human placenta

PROVIDER: PRJNA814711 | ENA |

REPOSITORIES: ENA

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	SRR18293083.fastq.gz	Fastqsanger.gz
	SRR18293086.fastq.gz	Fastqsanger.gz

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Regionally distinct trophoblast regulate barrier function and invasion in the human placenta.

Project description:The human placenta contains two specialized regions: the villous chorion where gases and nutrients are exchanged between maternal and fetal blood, and the smooth chorion (SC) which surrounds more than 70% of the developing fetus but whose cellular composition and function is poorly understood. Here, we use single cell RNA-sequencing to compare the cell types and molecular programs between these two regions in the second trimester human placenta. Each region consists of progenitor cytotrophoblasts (CTBs) and extravillous trophoblasts (EVTs) with similar gene expression programs. While CTBs in the villous chorion differentiate into syncytiotrophoblasts, they take an alternative trajectory in the SC producing a previously unknown CTB population which we term SC-specific CTBs (SC-CTBs). Marked by expression of region-specific cytokeratins, the SC-CTBs form a stratified epithelium above a basal layer of progenitor CTBs. They express epidermal and metabolic transcriptional programs consistent with a primary role in defense against physical stress and pathogens. Additionally, we show that SC-CTBs closely associate with EVTs and secrete factors that inhibit the migration of the EVTs. This restriction of EVT migration is in striking contrast to the villous region where EVTs migrate away from the chorion and invade deeply into the decidua. Together, these findings greatly expand our understanding of CTB differentiation in these distinct regions of the human placenta. This knowledge has broad implications for studies of the development, functions, and diseases of the human placenta.

| S-EPMC9323019 | biostudies-literature

Regionally distinct trophoblast regulate barrier function and invasion in the human placenta

Project description:Single Cell RNA-sequencing data from four human placental samples

2022-03-21 | GSE198373 | GEO

Myostatin Increases Trophoblast Cell Invasion Through Regulating Epithelial Mesenchymal Transition Genes

Project description:Myostatin (MSTN) is a TGF-β superfamily member and was recently shown to be secreted and functioning in the placenta. In this study, we perfomed mRNA sequencing on control and MSTN-treated primary trophoblast cells to decipher the underlying molecular mechanisms involved in MSTN-induced human trophoblast cell invasion.

2023-02-18 | GSE225378 | 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

VE-cadherin is essential for trophoblast migration and endovascular invasion

Project description:Vascular endothelial (VE-)cadherin is a homotypic adhesion protein that is expressed selectively by ECs in which it enables formation of tight vessels and regulation of vascular permeability. Since VE-cadherin is also strongly expressed in placental trophoblasts, it is a prime candidate for a molecular mechanism of vascular mimicry by those cells. Here, we show that the VE-cadherin is required for trophoblast migration and endovascular invasion into the maternal decidua. VE-cadherin deficiency results in loss of spiral artery remodeling due to a lack of invasive trophoblasts, leading to decreased flow of maternal blood into the placenta, fetal growth retardation and death. Loss of trophoblast invasion prevents decidualization, extracellular matrix remodeling, and immune cell clearance. These studies identify VE-cadherin as essential for trophoblast migration and coordination of decidual changes during endovascular invasion. They further suggest endothelial proteins such as VE-cadherin that are expressed by trophoblasts may play functionally distinct roles that do not simply mimic those in ECs.

2021-11-30 | GSE189408 | GEO

Trophoblast epithelial-mesenchymal transition (EMT) in abnormally invasive placenta (AIP)

Project description:Comparison of genes associated with the EMT between cytotrophoblast cells (CTB) and extravillous trophoblast cells (EVT) from normal third trimester placenta and abnormally invasive placenta (AIP)

2018-01-01 | GSE104350 | GEO

Breaking the first lineage barrier: Direct induction of trophoblast stem cells from murine fibroblasts

Project description:Trophoblast stem cells represent the stem cell population of the extra-embryonic lineage and arise as a result of the first cell fate decision. From blastocyst stage onwards, a distinct epigenetic lineage barrier strictly separates mouse embryonic and extra-embryonic lineages. Recently, it has been shown that this epigenetic barrier cannot be fully overcome as the expression of TS-determining factors in embryonic stem cells lead to incomplete transdifferentiation. Here, we demonstrate that transient expression of Tfap2c, Gata3, Eomes and Ets2 in fibroblasts suffices to generate cells which are almost identical to trophoblast stem cells based on morphology, expression and methylation pattern. Further, these induced trophoblast stem cells display transgene independent self-renewal, differentiate along the extra-embryonic lineage and chimerize the placenta upon blastocyst injection. Our findings provide insights into the transcription factor networks governing trophoblast stem cell identity and offer a new tool for studying the hierarchy of those factors.

2015-10-01 | GSE64145 | GEO

Breaking the lineage barrier: Direct induction of trophoblast stem cells from murine fibroblasts

Project description:Trophoblast stem cells represent the stem cell population of the extraembryonic lineage and arise as result of the first cell fate decision. From the blastocyst stage onwards, the extraembryonic lineage is strictly separated from the embryonic lineage by a distinct epigenetic lineage barrier. Recently, it has been shown, that this epigenetic barrier cannot be fully overcome as the expression of TS-determining factors in embryonic stem cells lead to incomplete trans-differentiation. Here we demonstrate that transient expression of Tfap2c, Gata3, Eomes and Ets2 in fibroblasts suffices to generate cells, which are almost equivalent to trophoblast stem cells based on morphology, expression and methylation patterns. Further, these induced trophoblast stem cells display self-renewal without exogenous factor expression, differentiate along the extraembryonic lineage and chimerize the placenta upon blastocyst injection. Our findings provide insights into transcription factor networks governing TSC identity and offer a new tool for studying the hierarchy of those factors.

2015-10-01 | GSE64339 | 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

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