Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA359418 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5136290.fastq.gz | Fastqsanger.gz | |||
| SRR5136300.fastq.gz | Fastqsanger.gz | |||
| SRR5136310.fastq.gz | Fastqsanger.gz | |||
| SRR5136320.fastq.gz | Fastqsanger.gz | |||
| SRR5136291.fastq.gz | Fastqsanger.gz |
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Project description:Cell-to-cell communication is essential for the spiral artery (SpA) remodeling and required for maternal transfer of nutrient and oxygen to the fetus. Extravillous trophoblast invade the uterine arteries to remodel the SpA during the first 20 weeks of gestation. Interestingly, oxygen tenstion in the uterine environment changes with the progression of pregnancies and damage in the SpA remodelling can lead to preeclampsia and pther pregnancy complications. Recently, our understanding of how cells communicate has undergone a paradigm shift since the recognition of the role of exosomes on intercellular signaling. Here, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT), modifying their bioactivity on endothelial cells. Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE) and spontaneous preterm birth (SPTB). The effect of oxygen tension (i.e. 8% and 1% oxygen) on exosome release was quantified using nanocrystals (Qdot®) coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte™) was used to establish the effect of exosomes on endothelial cells. Plasma samples were obtained at early gestation (<18 weeks) and classified according to pregnancy outcomes. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from exosomal RNA obtained from EVT and plasma samples. The number of exosomes was significantly hifger in EVT culturedunder 1% compared to 8% oxygen. In total, 741 miRNA were identified in exosomes from EVT. Bioinformatic analysis revealed that these miRNA were associated with cell migration and cytokine production. Interestingly, exosomes isolated from EVT cultured at 8% oxygen increased EC migration, while exosomes from 1% oxygen decrease EC migration. These changes were inversely proportional to TNF-α released from EC. Finally, we have identified a set of uniques miRNA in exosomes from EVT cultured at 1% oxygen and exosomes isolated from maternal at early gestation, who developed PE and SPTB later in pregnancy. We suggest that aberrant exosomal signalling by placental cells is a common aetiological factor in pregnancy complications characterised by incomplete SpA remodeling and is therefore a clinically useful biomarker of pregnancy complications.
2017-06-14 | GSE93020 | GEO
Project description:Invasive extravillous trophoblasts (EVTs) of the human placenta are critically involved in successful pregnancy outcome since they remodel the uterine spiral arteries to increase blood flow and oxygen delivery to the placenta and the developing fetus. To gain more insights into their biological role different primary cell culture models are commonly utilised. However, access to early placental tissue may be limited and primary trophoblasts rapidly cease proliferation in vitro impairing genetic manipulation. Hence, trophoblastic cell lines have been widely used as surrogates to study EVT function. Although the cell lines share some molecular marker expression with their primary counterpart, it is unknown to what extent they recapture the invasive phenotype of EVT. Therefore, we here report the first thorough GeneChip analyses of SGHPL-5, HTR-8/SVneo, BeWo, JEG-3 and the novel ACH-3P trophoblast cells in comparison to previously analysed primary villous cytrophoblasts and extravillous trophoblasts. To identify EVT-specific gene expression signatures in trophoblast cell lines, we calcuted differentially expressed genes between pre-defined groups based on the distinct origins of the five trophoblast cell lines under investigation. Comparison 1 comprised EVT, HTR-8/Svneo and SGHPL-5 vs choriocarcinoma cells (ACH-3P, BeWo, JEG-3). Comparison 2 comprised EVT, ACH-3P, BeWo, JEG-3 vs extravillous trophoblast cell lines (HTR-8/SVneo, SGHPL-5).
2010-09-23 | E-GEOD-20510 | biostudies-arrayexpress
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
Project description:Early placenta development involves cytotrophoblast differentiation into extravillous trophoblast (EVT) and syncytiotrophoblast (STB). Defective trophoblast development and function may result in severe pregnancy complications, including fetal growth restriction and pre-eclampsia. The incidence of these complications is increased in pregnancies of fetuses affected by Rubinstein–Taybi syndrome, a developmental disorder predominantly caused by heterozygous mutations in CREB-binding protein (CREBBP) or E1A-binding protein p300 (EP300). Although the acetyltransferases CREBBP and EP300 are paralogs with many overlapping functions, the increased incidence of pregnancy complications is specific for EP300 mutations. We hypothesized that these complications have their origin in early placentation and that EP300 is involved in that process. Therefore, we investigated the role of EP300 and CREBBP in trophoblast differentiation, using human trophoblast stem cells (TSCs) and trophoblast organoids. We found that pharmacological CREBBP/EP300 inhibition blocks differentiation of TSCs into both EVT and STB lineages, and results in an expansion of TSC-like cells under differentiation-inducing conditions. Specific targeting by RNA interference or CRISPR/Cas9-mediated mutagenesis demonstrated that knockdown of EP300 but not CREBBP, inhibits trophoblast differentiation, consistent with the complications seen in Rubinstein–Taybi syndrome pregnancies. By transcriptome sequencing, we identified transforming growth factor alpha (TGFA, encoding TGF-α) as being strongly upregulated upon EP300 knockdown. Moreover, supplementing differentiation medium with TGF-α, which is a ligand for the epidermal growth factor receptor (EGFR), likewise affected trophoblast differentiation and resulted in increased TSC-like cell proliferation. These findings suggest that EP300 facilitates trophoblast differentiation by interfering with at least EGFR signaling, pointing towards a crucial role for EP300 in early human placentation.
2023-12-19 | GSE250424 | GEO
Project description:Successful placentation requires delicate communication between endometrium and trophoblasts. The invasion and integration of trophoblasts into the endometrium during early pregnancy is crucial to placentation. Dysregulation of these functions is associated with various pregnancy complications such as miscarriage and preeclampsia. The endometrial microenvironment exerts an important influence on trophoblast cell functions. We hypothesized that the hormonal environment regulates the miRNA profile and secretome of the human endometrial gland, which subsequently modulates trophoblast functions during early pregnancy. By establishing the first secretome profiles and miRNA atlas of these endometrial organoids to the hormonal changes followed by trophoblast functional assays, we demonstrated that sex steroid hormones modulate aquaporins (AQP)1/9 and S100A9 secretions through miR-3194 activation in endometrial epithelial cells, which in turn enhanced trophoblast migration and invasion during early pregnancy.
2023-05-10 | PXD036535 | Pride
Project description: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.
2018-03-18 | GSE106852 | GEO
Project description:The placenta is a transient but important multifunctional organ crucial for healthy pregnancy for both mother and fetus. Nevertheless, limited access to human placenta samples and the paucity of a proper in vitro model system has hampered our understanding of the mechanisms underlying early human placental development and placenta-associated pregnancy complications. To overcome these constraints, we established a simple procedure with a short-term treatment of bone morphogenetic protein 4 (BMP4) in trophoblast stem cell culture medium (TSCM) to convert human primed pluripotent stem cells (PSCs) to trophoblast stem-like cells (TSLCs). These TSLCs show not only comparable morphology and gene expression profile to bona fide human trophoblast stem cells (TSCs) but also long-term self-renewal capacity with bipotency that allows the cells to differentiate into extravillous trophoblasts (EVT) and syncytiotrophoblasts (ST). These indicate that TSLCs are equivalent to genuine human TSCs. Our data suggest a straightforward approach to make human TSCs directly from pre-existing primed PSCs and provide a valuable opportunity to study human placenta development and pathology even from patients with placenta-related diseases.
2021-12-31 | GSE178162 | GEO
Project description:Hyperhomocysteinemia (HHcy) causes cardiovascular dysfunction and is associated with many complications during pregnancy related to reduced NO bioactivity. The mechanisms of HHcy on the NO-dependent control of myocardial metabolism was compared with L-NAME, which directly inhibits NO bioavailability, treated animals. We used microarrays to detail the global programme of gene expression underlying hyperhomocysteinemia during pregnancy and identified distinct classes of differentially regulated genes. Female SD rats were mated with male SD rats. Methionine was used to generate hyperhomocysteinemia model. L-NAME was used to generate NO restricted model. After treatment, the left ventricles were harvested for RNA extraction and hybridization on Affymetrix microarrays.
2015-06-12 | E-GEOD-30308 | biostudies-arrayexpress
Project description:Hyperhomocysteinemia (HHcy) causes cardiovascular dysfunction and is associated with many complications during pregnancy related to reduced NO bioactivity. The mechanisms of HHcy on the NO-dependent control of myocardial metabolism was compared with L-NAME, which directly inhibits NO bioavailability, treated animals. We used microarrays to detail the global programme of gene expression underlying hyperhomocysteinemia during pregnancy and identified distinct classes of differentially regulated genes.
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Project description:Preeclampsia (PE) is a peculiar multisystemic disorder that contributes to maternal and perinatal morbidity. Exosomes, existing in the circulation, origin from late endosomes which are secreted into the extracellular surrounding by diverse cell types under different conditions, can mediate intercellular communication via transporting its constituents and regulate inflammation, immunomodulation and angiogenesis. We hypothesize that exosomes from trophoblast in preeclampsia complications under pathological hypoxia microenvironment impair vascular development by transmitting its contents to endothelial cells. Here, transwell and tube formation assays revealed that exosomes from hypoxic trophoblast cells attenuated the migration, and tube formation in human umbilical vein endothelial cells (HUVECs) in vitro. In a mouse model, hypoxic trophoblast cells derived exosomes leaded to vascular dysfunction and caused adverse PE-like birth outcomes. Next, we detected lncRNA expression in cord blood plasma derived exosomes from gestational age-matched preeclampsia and normal pregnancies by microarray analysis. Then, we identified the possible mechanisms of one up-regulated exosomal lncRNA, TINCR. Application of Quantitative RT-PCR, lncTINCR was confirmed overexpressing in exosomes released from cord blood plasma, peripheral blood plasma and human placental trophoblasts of preeclampsia patients. Moreover, the exosomal lncTINCR could be specifically secreted by hypoxic trophoblast cells and transferred to HUVECs, which increased autophagy in HUVECs and impaired angiogenesis of endothelial cells in vitro. Furthermore, we demonstrated that lncTINCR was considered as a competing endogenous RNA to regulate miR-424, which resulted in elevated ATG5 expression. Thus, we reported that exosomes intervened effective delivering of lncTINCR to endothelial cells to damage vascular functions and result in the development of PE. The newly identified exosomal lncTINCR /miR-424/ATG5 axis may present potential novel targets of diagnosis and treatment for PE. lncRNA profiles of cord blood plasma derived exosomes from gestational age-matched preeclampsia and normal pregnancies
2024-09-02 | GSE183466 | GEO