Placental cytotrophoblast microvillar stabilization is required for cell-cell fusion
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1170338 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30914068_1.fastq.gz | Fastqsanger.gz | |||
| SRR30914068_2.fastq.gz | Fastqsanger.gz | |||
| SRR30914069_1.fastq.gz | Fastqsanger.gz | |||
| SRR30914069_2.fastq.gz | Fastqsanger.gz | |||
| SRR30914070_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 40 |
Similar Datasets
Project description:The placenta is an essential organ of pregnancy required for maternal-fetal transport and communication. The surface of the placenta facing the maternal blood is formed by a single giant multinucleate cell: the syncytiotrophoblast. The syncytiotrophoblast is formed and maintained via fusion of progenitor cytotrophoblasts. Cell-cell fusion is a tightly regulated process, and in non-trophoblastic cells is accompanied by stereotypical alterations in cell shape by cells that have attained fusion-competence. The most prominent feature is the formation of actin-based membrane protrusions, but whether stereotypic morphological changes occur in fusion-competent cytotrophoblasts has not been characterized. Using a human placental explant model and trophoblast organoids, we identify apical microvilliation as an obligate morphological feature of fusion-competent cytotrophoblasts. Disruption of microvilli using an inhibitor of the actin-membrane cross linker protein ezrin prevented cytotrophoblast fusion and differentiation. We provide evidence that these polarized apical microvillar domains function to regulate polarized endocytosis and to spatially localize and accumulate a key glycoprotein for fusion, CD98. Thus, we propose that the polarized assembly of microvillar domains is critical for mediating efficient syncytiotrophoblast development.
2025-03-26 | GSE279087 | GEO
Project description:Human cytotrophoblast organoid cultures were established from the villous trophoblast of first trimester placentas. We analyzed the global expression profile of the cytotrophoblast organoids (CTB-ORG) and compared to the profile of the tissue of origin i.e. villous cytotrophoblast (vCTB) as well as to differentiated syncytiotrophoblast (STB) and placental fibroblasts (FIB).
2018-08-02 | GSE109976 | GEO
Project description:Embryonic and extraembryonic development quickly diverges. Other than a globally hypomethylated genome, little is known about the epigenetic changes of placental cells throughout gestation. We profiled DNA methylation and activating/repressing histone modifications of cytotrophoblasts and four extraembryonic compartments in 2nd trimester and at term. Unexpectedly, in cytotrophoblasts, H3K9me3 occupancy precisely overlapped domains with more pronounced DNA hypomethylation and repressed transcription. At term, immunoblotting and -localization revealed extensive depletion of this and other histone modifications that paralleled increased genome-wide DNA methylation, which included hundreds of promoters. Candidate enhancers within embryonic stem cell differentially methylated regions (DMRs) revealed pluripotency factors, while those within cytotrophoblast DMRs revealed transcription factor binding motifs and genes that regulate placental development. DNA methylation, RNA, and miRNA profiling of the extraembryonic compartments identified regional specializations and gestational age regulation. Cytotrophoblast mRNAs that were down-regulated at term were enriched for genes up-regulated in severe preeclampsia. Correspondingly, immunoanalyses of cytotrophoblast histone modifications showed strong H3K27ac upregulation in severe preeclampsia. Thus, as gestation proceeded, certain cytotrophoblast histone modifications declined precipitously while, in pregnancy complications, these normal patterns were markedly perturbed. These data suggested an unusual genome-scale pattern of alterations in the abundance of histone modifications over the lifetime of the placenta. Marked alterations in this pattern were associated with pregnancy complications, indicating a possible causative role.
2017-05-17 | GSE98938 | GEO
Project description:Placental Accreta Spectrum: Upregulated Cytotrophoblast DOCK4 Contributes to Over Invasion
| PRJNA561109 | ENA
Project description:During human pregnancy, placental cytotrophoblasts invade the uterus and its blood vessels, anchoring the progeny and rerouting maternal blood to the embryo/fetus. In preeclampsia, cytotrophoblast invasion is restricted and blood flow to the placenta is reduced. The causes of restricted cytotrophoblast invasion are unknown. Here, preeclampsia and control cytotrophoblasts were cultured for 48 h to allow differentiation/invasion. In various severe forms of preeclampsia ± intrauterine growth restriction, global transcriptional profiling revealed common aberrations in cytotrophoblast gene expression that resolved with culture. Villous cytotrophoblasts were isolated from preeclampsia placentas (PRE, n=5) and placentas of preterm labor patients without signs of infection (PTL, n=5), which served as gestation-matched controls. To better understand the CTB phenotype in the context of PE variants, we included patients with the most clinically significant forms of this condition that necessitated preterm delivery: women with severe PE ± intrauterine growth restrictions, PE with superimposed hypertension and HELLP syndrome (hemolysis, elevated liver enzymes; low platelet count). RNA was purified immediately after the cells were isolated (0 h) and after 12, 24 and 48 h in culture. The relative gene expression across the whole genome was profiled using the Affymetrix HG-U133Plus 2.0 GeneChip platform. Array quality was assesed using RMAExpress. One sample of preterm labor collected at 48h was omitted (39 arrays total). We used both LIMMA and maSigPro (R/Bioconductor) to determine differentially expressed genes.
2012-08-17 | E-GEOD-40182 | biostudies-arrayexpress
Project description:Human cytotrophoblast organoids
| PRJNA432503 | ENA
Project description:Introduction: In human placenta, alteration in trophoblast differentiation has a major impact on placental maintenance and integrity. Moreover, abnormal syncytial fusion seems to be implicated in the development of many complications including pre-eclampsia and intra-uterine growth restriction (IUGR). However, little is known about the mechanisms that control cytotrophoblast fusion into syncytiotrophoblast. BeWo cell line is commonly used to study placental function since it can be induced to form syncytium and secretes hormones. This fusion is triggered by cAMP or forskolin treatments. In contrast, JEG-3 cell line fails to undergo substantial fusion. Therefore, we will use BeWo and JEG-3 cells to identify a set of genes responsible of trophoblast fusion. Methods: BeWo and JEG-3 cells were treated with forskolin for 48 to induce fusion. RNA was extracted, hybridized to Affymetrix HuGene ST1.0 arrays and analyzed using system biology. Trophoblast differentiation was evaluated by real time PCR and immunocytochemistry analysis. Moreover, some of the identified genes were validated by real time PCR. Results: Our results identified a list of 32 altered genes in fused BeWo cells compared to JEG-3 cells after forskolin treatment. Among these genes, 4 were validated by real-time PCR including salt inducible Kinase 1 (SIK1) gene which is specifically upregulated in BeWo cells upon fusion. Moreover, using system biology analysis, SIK1 showed to be at the center of many biological and functional processes which suggest that it might play a major role in trophoblast differentiation. Conclusion: This study identified new target genes implicated in trophoblast fusion; a process implicated in the etiology of many pregnancy-related diseases such as preeclampsia, IUGR, and gestational diabetes.
2019-02-26 | GSE127170 | GEO
Project description:The commitment and differentiation of human placental progenitor cytotrophoblast (CT) cells are crucial for a successful pregnancy, but the underlying regulatory mechanism remains poorly understood. Here we identified the transcription factor (TF), Specificity protein 6 (SP6), as a human species-specific trophoblast lineage TF expressed in human placental CT cells. Using pluripotent stem cells as a model, we demonstrated that SP6 governs CT generation and the establishment of trophoblast stem cells (TSCs) and discovered msh homeobox 2 (MSX2) as the downstream effector in these events. Mechanistically, we showed that SP6 interacts with histone acetyltransferase P300 to modulate the landscape of H3K27ac at targeted regulatory elements, thereby favoring transcriptional activation and facilitating CT cell fate decisions and TSC maintenance. Our results established SP6 as a novel regulator of the human trophoblast lineage and implied its regulatory role in placental development and the pathogenies of placental diseases.
2024-03-11 | GSE236795 | GEO
Project description:The commitment and differentiation of human placental progenitor cytotrophoblast (CT) cells are crucial for a successful pregnancy, but the underlying regulatory mechanism remains poorly understood. Here we identified the transcription factor (TF), Specificity protein 6 (SP6), as a human species-specific trophoblast lineage TF expressed in human placental CT cells. Using pluripotent stem cells as a model, we demonstrated that SP6 governs CT generation and the establishment of trophoblast stem cells (TSCs) and discovered msh homeobox 2 (MSX2) as the downstream effector in these events. Mechanistically, we showed that SP6 interacts with histone acetyltransferase P300 to modulate the landscape of H3K27ac at targeted regulatory elements, thereby favoring transcriptional activation and facilitating CT cell fate decisions and TSC maintenance. Our results established SP6 as a novel regulator of the human trophoblast lineage and implied its regulatory role in placental development and the pathogenies of placental diseases.
2024-03-11 | GSE236794 | GEO
Project description:To distinguish DNA methylation (DNAm) from cell proportion changes in whole placental villous tissue research, we developed a robust cell type-specific DNAm reference to estimate cell composition. We collated new and existing cell type DNAm profiles quantified via Illumina EPIC or 450k microarrays. To estimate cell composition, we deconvoluted whole placental samples (n=36) with robust partial correlation based on the top 30 hyper- and hypomethylated sites identified per cell type. To test deconvolution performance, we evaluated RMSE in predicting principal components of DNAm variation in 204 external placental samples. We analyzed DNAm profiles (n=368,435 sites) from 12 cell types: cytotrophoblasts (n=18), endothelial cells (n=19), Hofbauer cells (n=26), stromal cells (n=21), syncytiotrophoblasts (n=4), six lymphocyte types (n=36), and nucleated red blood cells (n=11). Median cell composition was consistent with placental biology: 60.9% syncytiotrophoblast, 17.3% stromal, 8.8% endothelial, 3.7% cytotrophoblast, 3.7% Hofbauer, 1.7% nucleated red blood cells, and 1.2% neutrophils. Our expanded reference outperformed an existing reference in predicting DNAm variation (PC1, 15.4% variance explained, IQR=21.61) with cell composition estimates (RMSEP: 8.62 vs. 10.79, p-value<0.001). This cell type reference can robustly estimate cell composition from whole placental DNAm data to detect important cell types, reveal biological mechanisms, and improve causal inference.
2024-12-03 | GSE271697 | GEO