Dataset Information

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE243579 | GEO | 2024/03/27

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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.

Dataset Information

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

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets