Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparison of ITGA2+ trophoblast progenitors to VCT and EVT

ABSTRACT: During pregnancy, trophoblast cells in the placenta are the only fetal cells in direct contact with the maternal blood and decidua. They have many functions, including transport of nutrients and oxygen, remodelling the uterine arteries, and communicating with maternal cells. Despite their importance in development and in the success of pregnancy, little is known about human trophoblast progenitors and their differentiation. We identify a proliferative trophoblast niche at the base of cytotrophoblast cell columns in first trimester placentas that is characterised by integrin α2 (ITGA2) expression. Pulse-chase experiments with 5-Iodo-2′-deoxyuridine (IdU) imply that these cells can contribute to both villous and extravillous lineages. Importantly, these cells can be isolated by ITGA2 using flow cytometry and express genes from both VCT and EVT. Microarray shows that they display a unique gene signature including NOTCH signalling and mesenchymal characteristics. ITGA2 allows for the first time the study of a pure population of trophoblast progenitor cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE106852 | GEO | 2018/03/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptomic Drivers of Differentiation, Maturation, and Polyploidy in Human Extravillous Trophoblast [SNP array]

Project description:During pregnancy, normal extravillous trophoblast (EVT) invade the endomyometrium of the maternal uterus and remodel the spiral arteries to control blood supply and nutrient transfer. Recent reports have described first trimester EVT as polyploid and senescent. Here we extend these earlier reports by performing comprehensive profiling of the genomic organization and transcriptome of first trimester EVT and term EVT. We define pathways and gene regulatory networks involved in both initial differentiation and maturation of this important trophoblast lineage at the maternal-fetal interface. Our results suggest that like first trimester EVT, term EVT undergo senescence and endoreduplication, are primarily tetraploid, and lack high rates of copy number variations. Additionally, we have highlighted senescence and polyploidy-related genes, pathways, networks, and transcription factors that appeared to be important in normal EVT differentiation and maturation and have validated a critical role for the unfolded protein response in EVT differentiation.

2021-08-11 | GSE173369 | GEO

Transcriptomic Drivers of Differentiation, Maturation, and Polyploidy in Human Extravillous Trophoblast [RNA-seq]

2021-08-11 | GSE173323 | GEO

Comparison of ITGA2+ trophoblast progenitors to VCT and EVT

Project description:Comparison of ITGA2+ trophoblast progenitors to VCT and EVT

| PRJNA418184 | ENA

Human uterine Natural Killer cells regulate differentiation of extravillous trophoblast early in pregnancy - scRNA-seq data

Project description:We used trophoblast organoids differentiating to extravillous trophoblast (EVT) to study the effects of key cytokines secreted by uterine Natural Killer (uNK) cells on EVT behaviour. Specifically, we exposed the organoids to four uNK-derived cytokines (CSF1, CSF2, XCL1, CCL5) and collected cells at different time points along the EVT differentiation pathway for scRNA-seq. We observe enhanced EVT differentiation in cytokine-treated organoids demonstrated by the increased proportion of late EVT subtypes and regulation of related pathways such as epithelial-mesenchymal transition. Moreover, uNK cytokines affect other processes important during early pregnancy including dampening of inflammatory and adaptive immune responses, regulation of blood flow, and placental access to nutrients.

2024-01-10 | E-MTAB-13382 | biostudies-arrayexpress

Human uterine Natural Killer cells regulate differentiation of extravillous trophoblast early in pregnancy - bulk RNA-seq data

Project description:An allorecognition system depending on interactions between uterine Natural Killer (uNK) cells and placental extravillous trophoblast (EVT) during early pregnancy influences reproductive outcomes in humans. Our previous immunogenetic studies show that particular combinations of maternal Killer Immunoglobulin-like Receptors (KIR) in uNK cells with fetal HLA-C variants on EVT are associated with disorders of pregnancy, especially pre-eclampsia. To identify responses stimulated in uNK cells specifically when activating KIR (KIR2DS1) binds to C2+HLA-C, a combination protective against pre-eclampsia, we modelled KIR-HLA interactions by co-culturing uNK cells with the 721.221 HLA-null cell line transfected to express either C1+ or C2+HLA-C molecules, followed by transcriptome profiling by RNA sequencing. We detect the secretion of key cytokines by uNK cells under the protective combination between KIR2DS1 and C2+HLA-C.

2024-01-10 | E-MTAB-13379 | biostudies-arrayexpress

Activation of the interferon pathway in trophoblast cells infected with SARS-CoV-2

Project description:Infection with SARS-CoV-2 in pregnancy has been associated with poor maternal and neonatal outcomes and placental defects. The placenta, which acts as a physical and immunological barrier at the maternal/fetal interface, is not established until the end of the first trimester. Therefore, localized viral infection of the trophoblast compartment early in gestation could trigger an inflammatory response resulting in altered placental function and consequent suboptimal conditions for fetal growth and development. In this study, we investigated the effect of SARS-CoV-2 infection in early gestation placentae using placenta-derived human trophoblast stem cells (TSC), a novel in vitro model, and their extra-villous trophoblast (EVT) and syncytiotrophoblast (STB) derivatives. Consistent with host viral entry protein expression, SARS-CoV-2 was able to productively replicate in TSC-derived STB and EVT but not undifferentiated TSC. Both early EVT and STB elicited an interferon-mediated innate immune response similar to other cells infected with this virus. Therefore, we have also shown that placenta derived TSCs are a robust in vitro model to investigate the effect of this viral infection in the trophoblast compartment of the early placenta. Overall, these results suggest that SARS-CoV-2 infection in early gestation can adversely affect placental development and that might occur via directly infecting the differentiated trophoblast compartment, thus posing a higher risk for poor pregnancy outcomes.

2023-10-14 | GSE216484 | GEO

iPSC-based modeling of preeclampsia identifies defects in extravillous trophoblast differentiation

Project description:Preeclampsia (PE) is a hypertensive pregnancy disorder with increased risk of maternal and fetal morbidity and mortality. Abnormal extravillous trophoblast (EVT) development and function is considered to be the underlying cause of PE, but has not previously been modeled in vitro. We previously derived induced pluripotent stem cells (iPSC) from placentas of PE patients and characterized abnormalities in formation of syncytiotrophoblast and responses to changes in oxygen tension. In this study, we converted these primed iPSC to naïve iPSC, then derived trophoblast stem cells (TSC) and EVT to evaluate molecular mechanisms underlying PE. We found that primed (but not naïve) iPSC-derived PE-EVT have reduced surface HLA-G, blunted invasive capacity, and altered EVT-specific gene expression. These abnormalities correlated with promotor hypermethylation of genes associated with the epithelial-mesenchymal transition pathway, specifically in primed-iPSC derived PE-EVT. Our findings indicate that abnormal epigenetic regulation might play a role in the PE pathogenesis.

2024-03-27 | GSE243579 | GEO

Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts

Project description:Zika virus (ZIKV) infection at the maternal-placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be differentiated into early gestation syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT). TSCs and STs, but not EVTs, were highly permissive to productive infection with ZIKV strain DAK AR 41524. The impact of ZIKV on the cellular transcriptome showed that infection of TSCs and STs increased expression of immune related genes, including those involved in type I and type III interferon responses. ZIKV exposure altered extracellular vesicle (EV) protein, mRNA, and miRNA cargo, regardless of productive infection. These findings suggest that early gestation macaque TSCs and STs are permissive to ZIKV infection, and that EV analysis may provide a foundation for identifying non-invasive biomarkers of placental infection in a highly translational model.

2022-05-20 | PXD033289 | Pride

Single-Cell Gene Expression Analysis of First Trimester Placenta Samples Linked to Idiopathic Recurrent Pregnancy Loss

Project description:The extravillous trophoblast (EVT) cell lineage is a key feature of placentation and critical for spiral artery remodeling and successful pregnancy. Our knowledge of transcriptional regulation driving EVT cell development is limited. Here, we mapped the transcriptome and epigenome landscape as well as chromatin interactions of human trophoblast stem (TS) cells and their transition into the differentiated EVT cell lineage. Chromatin accessibility in intergenic regions was more extensive in EVT cells than in TS cells in the stem state, which is consistent with increased enhancer-driven gene regulation. Using reference epigenome annotation, we noted that 18% of the chromatin landscape in EVT cells was uncharted. We linked regulatory regions to their cognate target genes and characterized the three-dimensional organization of the TS cell functional genome by high throughput chromosome conformation capture. Integration of chromatin accessibility, long-range chromatin interactions, transcriptomic, and transcription factor binding motif enrichment enabled identification of transcription factors and regulatory mechanisms associated with EVT cell lineage development. Subsequent analyses elucidated functional roles for TFAP2C, SNAI1 and EPAS1 in the regulation of EVT cell lineage development. EPAS1 was identified as an upstream regulator of key EVT cell transcription factors, including ASCL2 and SNAI1 and was together with its targets linked to diseases of pregnancy, including idiopathic recurrent pregnancy loss and low birth weight. Collectively, we have revealed activation of a dynamic regulatory network that provides a framework for understanding EVT cell specification in trophoblast cell lineage development and human placentation.

2023-06-14 | GSE204723 | GEO

Global Epigenome and Transcriptome Maps of Human Trophoblast Cell Lineage Development [Hi-C]

Project description:The extravillous trophoblast (EVT) cell lineage is a key feature of placentation and critical for spiralartery remodeling and successful pregnancy. Our knowledge of transcriptional regulation driving EVT cell development is limited. Here, we mapped the transcriptome and epigenome landscape as well as chromatin interactions of human trophoblast stem (TS) cells and their transition into the differentiated EVT cell lineage. We identified that chromatin accessibility in intergenic regions was more extensive in EVT cells than in TS cells in the stem state, which is indicative of increased enhancer-driven gene regulation. Using reference epigenome annotation, we noted that 18% of the chromatin landscape in EVT cells was uncharted. We linked regulatory regions to their cognate target genes and characterized the three-dimensional organization of the TS cell functional genome by Hi-C. Integrational analysis of chromatin accessibility, long-range chromatin interactions, transcriptomic, and transcription factor binding motif enrichment enabled identification of transcription factors and regulatory mechanisms associated with EVT cell lineage development. Subsequent analyses elucidated functional roles forTFAP2C,EPAS1,SNAI1, andDLX6in the regulation of EVT cell lineage development.EPAS1was identified as an upstream regulator of EVT cell transcription factors, includingSNAI1andDLX6, and was found to be upregulated in idiopathic recurrent pregnancy loss. Collectively, we have revealed activation of a dynamic regulatory network that provides a framework for understanding EVT cell specification in trophoblast cell lineage development and human placentation.

2023-07-21 | GSE237677 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data