Histopathologic and transcriptome profiling identify novel trophoblast lineage-specific defects in preeclampsia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA773083 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16505203_1.fastq.gz | Fastqsanger.gz | |||
| SRR16505203_2.fastq.gz | Fastqsanger.gz | |||
| SRR16505204_1.fastq.gz | Fastqsanger.gz | |||
| SRR16505204_2.fastq.gz | Fastqsanger.gz | |||
| SRR16505205_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 88 |
Similar Datasets
Project description:Preeclampsia (PE) is a heterogeneous disease which lacks pathophysiology-based subclassification. Current clinical classification is based on gestational age at diagnosis and severity of disease. However, PE placentas have heterogeneous findings on pathologic exam. We combined clinical, pathological, immunohistochemical (IHC), and transcriptomic profiling to better subclassify this disease. 303 PE and 1388 non-hypertensive controls were included, with subgroups of samples used for each analysis. Detailed clinical and placental pathologic data were abstracted from our Obstetric Registry. Tissue studio (Definiens) was used for IHC analysis. RNAseq was performed using Illumina-NovaSeq using our standard pipeline. We found that maternal vascular malperfusion (MVM) in the placenta is associated with preterm PE and small-for-gestation neonates, with further subclassification into groups with and without fetal vascular malperfusion (FVM). Interestingly, MVM with FVM was further characterized by loss of proliferative cytotrophoblast, as confirmed by p63 IHC. Finally, transcriptomic analysis identified pathways associated with hypoxia and reduced cell-proliferation in PE-MVM placentas, and further subclassified this group into syncytiotrophoblast (STB)hi and extravillous trophoblast (EVT)hi PE, confirmed by IHC for trophoblast lineage-specific markers. Our findings suggest that PE can be subclassified based on underlying pathophysiologic changes, allowing identification of pathways which can be targeted for diagnostic and therapeutic purposes.
2023-01-10 | GSE186257 | GEO
Project description:iPSC-based modeling of preeclampsia identifies defects in extravillous trophoblast differentiation
| PRJNA1018965 | ENA
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:Diminished trophoblast differentiation in early onset preeclampsia
| PRJNA778240 | 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
Project description:The maternal signs of preeclampsia, principally the new onset of high blood pressure, are thought to occur secondary to faulty placentation. Previous studies profiled the gene expression patterns of chorionic villi, the maternal-fetal interface or isolated cytotrophoblasts in this pregnancy complication. We theorized that transcriptomic analyses of trophoblast subpopulations in situ would give us new insights into the role of these cells in preeclampsia pathogenesis.
2017-01-24 | GSE93839 | GEO
Project description:To explore the potential role of focal adhesion kinase (FAK) in trophoblast functions in early-onset preeclampsia (EOPE).We first examined expression and localization in placental tissue as well as in villus tissue during early pregnancy. Then, FAK activity was inhibited with Y15. The effects of FAK on the invasion and proliferation of trophoblast cells (HTR8/SVneo) were investigated. Transcriptomic and bioinformatics analyses were then used to predict the possible pathways by which FAK is involved in PE. Finally, we measured the expression of FAK in a PE mouse model. Transcriptomic and bioinformatics results suggest that Rap1 may be a downstream regulator of trophoblast FAK. In mouse models, we found reduced expression of FAK and Rap1 in the placenta of PE mice.
2025-07-10 | GSE271940 | GEO
Project description:In addition to being a potent tumor suppressor, the p53 protein (encoded by Trp53 in mouse and TP53 in human) has important functions in embryo development and stem cells. The Trp53-null mice exhibit developmental defects whereas p53 activation causes implantation failure. However, it remains unclear how p53 affects early embryonic cell lineage development. We report here that p53 is highly expressed in the trophectoderm (TE) of the blastocyst and that blocking p53 activities arrests preimplantation embryo development. We have subsequently investigated p53 using human pluripotent stem cells (hPSCs) in the generation of human trophoblast stem cells (hTSCs). Genetic ablation of TP53 or chemical inhibition of p53 activities hinders the generation of hTSCs while enhancing the generation of amniotic cells. Furthermore, p53 deficiency in hTSCs results in epigenetic dysregulation of the trophoblast regulatory network involving the generation of mature syncytiotrophoblasts (STBs). In contrast, the generation and invasiveness of extravillous trophoblasts (EVTs) is enhanced. Single-cell transcriptomics analysis and experimental investigation further revealed the importance of p53 functions at multiple stages of human trophoblast development and identify that p53-mediated cell-cycle state determines trophoblast cell fate propensity. These findings for the first time demonstrate the important functions of p53 in human early embryonic cell lineage development and implicate possible links between the role of p53 in early development and tumor suppression.
2025-09-22 | GSE277265 | GEO