Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1019896 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR26139400_1.fastq.gz | Fastqsanger.gz | |||
| SRR26139400_2.fastq.gz | Fastqsanger.gz | |||
| SRR26139401_1.fastq.gz | Fastqsanger.gz | |||
| SRR26139401_2.fastq.gz | Fastqsanger.gz |
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Project description:iPSC-based modeling of preeclampsia identifies defects in extravillous trophoblast differentiation
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Project description:Preeclampsia (PE) is a hypertensive disorder, which affects up to 10% of pregnancies worldwide. The primary etiology is considered to be abnormal development and function of placental cells called trophoblasts. We previously developed a two-step protocol for differentiation of human pluripotent stem cells, first into cytotrophoblast (CTB) progenitor-like cells, and then into both syncytiotrophoblast (STB)- and extravillous trophoblast (EVT)-like cells, and showed that this protocol can be used to model both normal and abnormal trophoblast differentiation. We have now applied this protocol to differentiate induced pluripotent stem cells (iPSC) derived from placentas of pregnancies with or without PE. While we did not note any differences in CTB induction, PE-iPSC-derived CTB showed a defect in syncytialization, and had a >180-fold reduction in expression of PSG4, a mature STB marker (p<0.02). While EVT formation did not appear to be altered, the invasive capacity of PE-iPSC-derived EVT was non-responsive to a decrease in oxygen tension, while that of non-PE-iPSC-derived EVT was enhanced 3.8-fold. RNA sequencing analysis showed gene expression changes consistent with defects in STB formation and response to hypoxia in PE-iPSC derived trophoblast. However, differences in DNA methylation were minimal, with only documented differences consistent with part of the response to hypoxia. Overall, PE-associated iPSC recapitulated multiple defects associated with placental dysfunction, with their lack of response to decreased oxygen tension emphasizing the importance of the interface with the maternal microenvironment in normal placentation.
2021-03-15 | GSE159479 | GEO
Project description:Preeclampsia (PE) is a hypertensive disorder, which affects up to 10% of pregnancies worldwide. The primary etiology is considered to be abnormal development and function of placental cells called trophoblasts. We previously developed a two-step protocol for differentiation of human pluripotent stem cells, first into cytotrophoblast (CTB) progenitor-like cells, and then into both syncytiotrophoblast (STB)- and extravillous trophoblast (EVT)-like cells, and showed that this protocol can be used to model both normal and abnormal trophoblast differentiation. We have now applied this protocol to differentiate induced pluripotent stem cells (iPSC) derived from placentas of pregnancies with or without PE. While we did not note any differences in CTB induction, PE-iPSC-derived CTB showed a defect in syncytialization, and had a >180-fold reduction in expression of PSG4, a mature STB marker (p<0.02). While EVT formation did not appear to be altered, the invasive capacity of PE-iPSC-derived EVT was non-responsive to a decrease in oxygen tension, while that of non-PE-iPSC-derived EVT was enhanced 3.8-fold. RNA sequencing analysis showed gene expression changes consistent with defects in STB formation and response to hypoxia in PE-iPSC derived trophoblast. However, differences in DNA methylation were minimal, with only documented differences consistent with part of the response to hypoxia. Overall, PE-associated iPSC recapitulated multiple defects associated with placental dysfunction, with their lack of response to decreased oxygen tension emphasizing the importance of the interface with the maternal microenvironment in normal placentation.
2021-03-15 | GSE159437 | GEO
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:Comparison of genes associated with the EMT between undifferentiated cytotrophoblast cells (CTB) and differentiated extravillous trophoblast cells (EVT) from third trimester human placenta. Cells isolated from control (placenta previa) and cases (preeclampsia). Cells isolated by immunomagnetic separation using anti-integrin beta4 antibody to purify CTB and anti-HLA-G antibody to purify EVT.
2022-02-26 | GSE188313 | GEO
Project description:In human, the functional placenta requires the proper differentiation of trophoblastic subtypes from the trophoblast stem cells (hTSCs). Although successful derivation of hTSCs from the early placentas and blastocysts, these hTSCs face ethical concerns and limited models for trophoblast-related disorders at later stage, such as preeclampsia. Here, we show that both hESCs and hiPSCs are able to be induced to the long-term and proliferative hTSCs under defined culture medium. These induced trophoblast stem cells (iTSCs) are comparable to the hTSC cell line derived from blastocyst in morphology, growth properties, specific genes expression, capacity of differentiating toward extravillous cytotrophoblast and syncytiotrophoblast, and patterns of transcriptome profile, chromatin accessibility and histone modification that are conducive to placenta development and maintenance of hTSCs. Notably, iTSCs meet four criteria defining "trophoblastic" including: expression of specific transcript factors, hypomethylation of ELF5 promoter, lack of expression of HLA-class I molecules and expression of the chromosome 19-encoded miRNA. Moreover, we reveal that addition of BMP4 or absence of H3K27 methyltransferases EZH1/2 could enhance the iTSCs generation. Our results suggest that human TS cells could be derived from human pluripotent stem cells, which expands the source of human TS cells avoiding ethic issues and provides a useful tool for researching placenta development and function, and modeling placenta-originated disorders.
2021-08-16 | GSE135694 | GEO
Project description:In human, the functional placenta requires the proper differentiation of trophoblastic subtypes from the trophoblast stem cells (hTSCs). Although successful derivation of hTSCs from the early placentas and blastocysts, these hTSCs face ethical concerns and limited models for trophoblast-related disorders at later stage, such as preeclampsia. Here, we show that both hESCs and hiPSCs are able to be induced to the long-term and proliferative hTSCs under defined culture medium. These induced trophoblast stem cells (iTSCs) are comparable to the hTSC cell line derived from blastocyst in morphology, growth properties, specific genes expression, capacity of differentiating toward extravillous cytotrophoblast and syncytiotrophoblast, and patterns of transcriptome profile, chromatin accessibility and histone modification that are conducive to placenta development and maintenance of hTSCs. Notably, iTSCs meet four criteria defining "trophoblastic" including: expression of specific transcript factors, hypomethylation of ELF5 promoter, lack of expression of HLA-class I molecules and expression of the chromosome 19-encoded miRNA. Moreover, we reveal that addition of BMP4 or absence of H3K27 methyltransferases EZH1/2 could enhance the iTSCs generation. Our results suggest that human TS cells could be derived from human pluripotent stem cells, which expands the source of human TS cells avoiding ethic issues and provides a useful tool for researching placenta development and function, and modeling placenta-originated disorders.
2021-08-16 | GSE135693 | GEO
Project description:Preeclampsia is associated with reduced ISG15 levels impairing extravillous trophoblast invasion.
| PRJNA719566 | ENA
Project description:Placentation requires the proper regulation of extravillous trophoblast (EVT) migration and invasion into the decidua and maternal vasculature, processes which are initiated in physiologic hypoxic conditions. Abnormal EVT migration and/or invasion have been suggested to lead to pregnancy complications, such as preeclampsia. The objectives of this study are to determine how exposure to hypoxia impacts gene expression and cellular motility of first trimester trophoblasts, and to assess if expression of migration-associated genes is dysregulated in 2nd trimester chorionic villous samples (CVS) from preeclampsia pregnancies relative to CVS from healthy pregnancies. The 1st trimester trophoblast cell line, HTR8/SVneo, was used to investigate the relationship between hypoxia and Notch signaling in trophoblast migration and invasion. RNA sequencing and quantitative RT-PCR analyses show that exposure to hypoxia (2.5% O2) activates Notch signaling in HTR-8/SVneo. We demonstrate that exposure of HTR-8/SVneo to hypoxia induces expression of genes associated with cellular migration and invasion and increases HTR-8/SVneo cellular migration and invasion, whereas inhibition of gamma-secretase decreases Notch signaling and decreases HTR-8/SVneo migration and invasion. Analysis of RNA sequencing data from CVS of preeclampsia and uncomplicated pregnancies identified significant differentially expressed genes that are involved in cellular migration and invasion. Decreased expression of migration and invasion genes in CVS from preeclampsia pregnancies, may impair trophoblast migration and invasion in the 2nd trimester of pregnancy, resulting in the development of preeclampsia.
2021-08-05 | GSE155750 | GEO
Project description:Invasive trophoblast cells are critical to spiral artery remodeling in hemochorial placentation. Insufficient trophoblast invasion and vascular remodeling can lead to pregnancy disorders including preeclampsia, preterm birth, and intrauterine growth restriction. Previous studies in the mouse identified achaete-scute homolog 2 (ASCL2) as essential to extraembryonic development. We hypothesized that ASCL2 is a critical and conserved regulator of invasive trophoblast lineage development. In contrast to the mouse, the rat possesses deep intrauterine trophoblast cell invasion and spiral artery remodeling similar to human placentation. In this report, we investigated invasive/extravillous trophoblast (EVT) cell differentiation using human trophoblast stem (TS) cells and a loss-of-function mutant Ascl2 rat model. ASCL2 transcripts are expressed in the EVT column and junctional zone, which represent tissue sources of invasive trophoblast progenitor cells within human and rat placentation sites, respectively. Differentiation of human TS cells into EVT cells resulted in significant upregulation of ASCL2 and several other transcripts indicative of EVT cell differentiation. Disruption of ASCL2 impaired EVT cell differentiation as indicated by cell morphology and transcript profiles. RNA sequencing analysis of ASCL2-deficient trophoblast cells identified both downregulation of EVT cell-associated transcripts and upregulation of syncytiotrophoblast-associated transcripts, indicative of dual activating and repressing functions. ASCL2 deficiency in the rat impacted placental morphogenesis resulting in junctional zone dysgenesis and failed intrauterine trophoblast cell invasion. ASCL2 acts as a critical and conserved regulator of invasive trophoblast cell lineage development and a species-specific modulator of the syncytiotrophoblast lineage.
2021-03-01 | GSE154350 | GEO