To identify GCM1 novel target genes by chromatin immunoprecipitation-on-chip (ChIP-chip) analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE158894 | GEO | 2021/06/11
REPOSITORIES: GEO
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Project description:The placenta plays an important role as a regulator of fetal nutrition and growth throughout development and placental factors contribute to gestational abnormalities such as preeclampsia. This study describes the genome-wide gene expression profiles of a large (n=60) set of human placentas in order to uncover gene expression patterns associated with preeclampsia. In addition to confirming changes in expression of soluble factors associated with preeclampsia such as sFLT1 (soluble fms-like tyrosine kinase-1), sENG (soluble endoglin), and INHA (inhibin alpha), we also find changes in immune-associated signaling pathways, offering a potential upstream explanation for the shallow trophoblast invasion and inadequate uterine remodeling typically observed in pathogenesis of preeclampsia. Notably, we also find evidence of preeclampsia-associated placental upregulation of sialic acid acetylesterase (SIAE), a gene functionally associated with autoimmune diseases. 23 preeclamptic, and 37 control placentas included in this study were collected during the years of 2004-2008 and hybridized in two batches to microarrays. Samples were randomized across arrays to control for array and batch variability.
2010-12-10 | E-GEOD-25906 | biostudies-arrayexpress
Project description:The placenta plays an important role as a regulator of fetal nutrition and growth throughout development and placental factors contribute to gestational abnormalities such as preeclampsia. This study describes the genome-wide gene expression profiles of a large (n=60) set of human placentas in order to uncover gene expression patterns associated with preeclampsia. In addition to confirming changes in expression of soluble factors associated with preeclampsia such as sFLT1 (soluble fms-like tyrosine kinase-1), sENG (soluble endoglin), and INHA (inhibin alpha), we also find changes in immune-associated signaling pathways, offering a potential upstream explanation for the shallow trophoblast invasion and inadequate uterine remodeling typically observed in pathogenesis of preeclampsia. Notably, we also find evidence of preeclampsia-associated placental upregulation of sialic acid acetylesterase (SIAE), a gene functionally associated with autoimmune diseases.
2010-12-10 | GSE25906 | GEO
Project description:We have designed an implantation-on-a-chip device to model the invasion of specialized fetal extravillous trophoblasts (EVTs) from an implanting embryo into the maternal decidua. We profiled the cellular proteome of sorted EVTs or endothelial cells from devices containing different cell compositions: 1) EVTs monoculture, 2) Endothelial cells monoculture, and 3) EVTs and endothelial cells co-cultured. The proteins were extracted using the MPLEx extraction method (Nakayasu et. al. PMCID: PMC5069757), digested with 1:50 (trypsin:protein, w:w) for 3 hr at 37 C. Solid phase extraction (SPE) was performed on the samples using 1 mL/50 mg columns from Phenomenex as previously described (PMCID: PMC7192326). Peptidic concentration was assayed using a BCA assay and 5 ul at 0.1 ug/ul were injected on the LC-MS/MS system. Data was searched with MaxQuant.
2022-01-12 | MSV000088677 | MassIVE
Project description:Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. Within the basal plate, placental cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel the maternal vasculature. In PE, CTB invasion is often shallow, and vascular remodeling is rudimentary. To better understand possible causes, we conducted a global analysis of gene expression at the maternal-fetal interface in placental samples from women with PE (n = 12; 24-36 wk) vs. samples from women who delivered due to preterm labor with no evidence of infection (n = 11; 24-36 wk), a condition that our previous work showed is associated with normal CTB invasion. Using the HG-U133A&B Affymetrix GeneChip platform, and statistical significance set at log odds-ratio of B >0, 55 genes were differentially expressed in PE. They encoded proteins previously associated with PE [e.g. Flt-1 (vascular endothelial growth factor receptor-1), leptin, CRH, and inhibin] and novel molecules [e.g. sialic acid binding Ig-like lectin 6 (Siglec-6), a potential leptin receptor, and pappalysin-2 (PAPP-A2), a protease that cleaves IGF-binding proteins]. We used quantitative PCR to validate the expression patterns of a subset of the genes. At the protein level, we confirmed PE-related changes in the expression of Siglec-6 and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts. Notably, Siglec-6 placental expression is uniquely human, as is spontaneous PE. The functional significance of these novel observations may provide new insights into the pathogenesis of PE, and assaying the circulating levels of these proteins could have clinical utility for predicting and/or diagnosing PE. Keywords: disease state analysis Basal plate biopsies of preterm labor (24-36 weeks; n=11) and preterm severe preeclampsia (24-36 weeeks; n=12) were isolated and the global gene expression profiles determined using Affymetrix Human GeneChips. Comparisons between the preeclampsia samples and the preterm labor controls revealed genes differentially expressed in preeclampsia.
2009-02-06 | E-GEOD-14722 | biostudies-arrayexpress
Project description:In this study, we identify SYDE1 as a novel GCM1 target gene. We demonstrate that SYDE1 promotes placental cell migration and invasion and that the GCM1-SYDE1 axis is crucial for placental development. Importantly, retarded placental and fetal growth with defective spongiotrophoblast layer, compromised vasculogenesis, and abnormal maternal-trophoblast interface are noted in the Syde1 homozygous knockout (KO) placenta. Along this line, decreased SYDE1 expression is observed in human IUGR placentas. We further demonstrated that components of the renin-angiotensin system (RAS) and Syde2 are differentially expressed in Syde1-KO placenta, which might contribute to normal neonatal delivery in Syde1-KO mothers
2016-10-18 | GSE81468 | GEO
Project description:Preeclampsia (PE), which affects ~8% of first pregnancies, is associated with faulty placentation. Extravillous cytotrophoblasts (CTBs) fail to differentiate properly, contributing to shallow uterine invasion and deficient spiral artery remodeling. We studied the effects of severe PE (sPE) on the smooth chorion portion of the fetal membranes. The results showed a significant expansion of the CTB layer. The cells displayed enhanced expression of stage-specific antigens that extravillous CTBs normally up regulate as they exit the placenta. Transcriptomics revealed the dysregulated expression of many genes (e.g., placental proteins, markers of oxidative stress). We confirmed a sPE-related increase in production of PAPPA1, which releases IGF-1 from its binding protein. IGF1 enhanced proliferation of smooth chorion CTBs (schCTB), a possible explanation for expansion of this layer, which may partially compensate for the placental deficits.
2016-12-10 | GSE91189 | GEO
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:Background; Mutations in STOX1 were proposed as causal for predisposing to preeclampsia, a hypertensive disorder originating from placental defects, affecting up to 10% of human pregnancies. However, after the first study published in 2005 three other groups have dismissed the polymorphism described in the first paper as a causal mutation. Methodology and Principal Findings; In the present study, we have developed a choriocarcinoma cell line overexpressing STOX1. This overexpression results in the transcriptional modification of 12.5% of the genes, some of them being direct targets as shown by chromatin immunoprecipitation. STOX1 overexpression correlates strongly and specifically with transcriptomic alterations in preeclamptic placentas (r=0.30, p=9.10-7). Numerous known key modulators of preeclampsia (such as Endoglin, Syncytin, human chrionic gonadotrophin-hCG-, and Glial Cell Missing Homolog -GCM1-) were modified in these transformed choriocarcinoma cells. Conclusions; Our results contribute to reconcile contradictory data about the involvement of STOX1 in preeclampsia. In addition, they strongly suggest that anomalies in STOX1 expression are associated with the onset of preeclampsia, thus indicating that this gene should be the target of future studies. Furthermore, our cellular model could constitute an invaluable resource for studying specific aspects of this human disease. Experiment Overall Design: Microarrays expression
2008-11-14 | E-GEOD-13475 | biostudies-arrayexpress
Project description:Preeclampsia complicates more than 3% of all pregnancies in the United States and Europe. High-risk populations include women with diabetes, dyslipidemia, thrombotic disorders, hyperhomocysteinemia, hypertension, renal diseases, previous preeclampsia, twin pregnancies, and low socioeconomic status. In the latter case, the incidence may increase to 20% to 25%. Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Preeclampsia is defined by systolic blood pressure of more than 140 mm Hg and diastolic blood pressure of more than 90 mm Hg after 20 weeks gestation in a previously normotensive patient, and new-onset proteinuria. Abnormal placentation associated with shallow trophoblast invasion (fetal cells from outer cell layer of the blastocyst) into endometrium (decidua) and improper spiral artery remodeling in the decidua are initial pathological steps. In this study we analyzed the renin-angiotensin system in adipose tissue, decidua and placenta from women with uneventful pregnancy and women with preeclampsia. We also analyzed the tissue by Affymetrix chips in a comparison study (control vs. preeclampsia) Experiment Overall Design: 6 affymetrix human expression chips (GPL570) were analyzed. Experiment Overall Design: They represent 3 tissues (pooled from 10 individuals each) from patients with preeclampsia and from patients with uneventful pregnancy (collected by cesaraen section). Tissues from patients with uneventful pregnancy are the controls in comparison to tissues of patients with preeclampsia.
2008-06-14 | E-GEOD-6573 | biostudies-arrayexpress
Project description:Preeclampsia complicates more than 3% of all pregnancies in the United States and Europe. High-risk populations include women with diabetes, dyslipidemia, thrombotic disorders, hyperhomocysteinemia, hypertension, renal diseases, previous preeclampsia, twin pregnancies, and low socioeconomic status. In the latter case, the incidence may increase to 20% to 25%. Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Preeclampsia is defined by systolic blood pressure of more than 140 mm Hg and diastolic blood pressure of more than 90 mm Hg after 20 weeks gestation in a previously normotensive patient, and new-onset proteinuria. Abnormal placentation associated with shallow trophoblast invasion (fetal cells from outer cell layer of the blastocyst) into endometrium (decidua) and improper spiral artery remodeling in the decidua are initial pathological steps. In this study we analyzed the renin-angiotensin system in adipose tissue, decidua and placenta from women with uneventful pregnancy and women with preeclampsia. We also analyzed the tissue by Affymetrix chips in a comparison study (control vs. preeclampsia) Keywords: disease comparison, disease state
2007-01-01 | GSE6573 | GEO