Analysis of differentially expressed genes in placental tissues of Pre-eclampsia Using microarray combined with Connectivity Map database
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE47187 | GEO | 2013/10/01
SECONDARY ACCESSION(S): PRJNA205045
REPOSITORIES: GEO
Similar Datasets
Project description:Preeclampsia (PE), which affects 2-7% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. To better understand the pathophysiology of PE, gene expression profiling of placental tissue from 5 controls and 5 PEs were assessed using microarray. A total of 224 transcripts were identified as being significantly differentially expressed (fold change > 2 and q value < 0.05 in the SAM software), GO enrichment analysis indicated that genes involved hypoxia, oxidative and reductive processes were significantly changed. Ten differentially expressed genes (DEGs) involved in these biological process were further verified by quantitative real-time PCR. Finally, the potential therapeutic agents for PE were explored via Connectivity Map database . In conclusion, the data obtained in this study might provide clues to better understand the pathophysiology of PE and found potential therapeutic agents for PE patients. gene expression profiling of placental tissue from 5 controls and 5 PEs were assessed using microarray.
2013-10-01 | E-GEOD-47187 | biostudies-arrayexpress
Project description:Preeclampsia (PE) is characterized by sustained hypertension and proteinuria at a gestational age of 20 weeks or more. Immune system alterations are associated with the origin and the pathophysiology of preeclampsia, however, little is known about the landscape and heterogeneity of maternal immune system at the single-cell level. In this study, we performed single-cell RNA sequencing of 80,429 cells in PE patients and health controls, including T cells, B cells, natural killer (NK) cells, myeloid cells in peripheral blood mononuclear cells to characterize the immune cell subgroups at the pregnant and postpartum stages of PE. Our work showed that there was excessive activation of B cells, monocytes and NK cells in PE patients at the pregnant stage. Additionally, lower immune response activation was noticed in CD4+ and CD8+ T cells in PEs, especially the low-activation of memory T cells at the pregnant and postpartum stages. Moreover, there was a higher activation of B cells in pregnancy persisted postpartum in PEs, together with lower activation of memory T cells. These indicated their persistent effects on PE and its recurrence risks.
2022-11-15 | GSE192693 | GEO
Project description:Background: Preeclampsia (PE) is a multi-systemic maternal syndrome with substantial maternal and fetal morbidity and mortality. Currently, there is no clinically viable non-invasive biomarker assay for early detection, thus limiting the effective prevention and therapeutic strategies for PE. Methods: We conducted a discovery-training-validation three-phase retrospective and prospective study with cross-platform and multicenter cohorts. The initial biomarkers were discovered and verified in tissue specimens by small RNA sequencing and qRT-PCR. A miRNA signature (miR2PE-score) was developed using the Firth’s bias-reduced logistic regression analysis, and subsequently validated in two independent multinational retrospective cohorts and two prospective plasma cohorts. Results: We initially identified five PE-associated differentially expressed miRNAs from miRNA sequencing data and subsequently validated two miRNAs (miR-196b-5p and miR-584-5p) as robust biomarkers by association analysis with clinical characteristics and qRT-PCR in tissue specimens in the discovery phase. Using the Firth’s bias-reduced logistic regression analysis, we developed the miR2PE-score for the early detection of PE. The miR2PE-score showed a high diagnostic performance with an area under the receiver operating characteristic curve (AUROC) of 0.920, 0.848, 0.864 and 0.812 in training, internal and two external validation cross-platform and multicenter cohorts, respectively. Finally, we demonstrated the non-invasive diagnostic performance of the miR2PE-score in two prospective plasma cohorts with AUROC of 0.933 and 0.787. Furthermore, the miR2PE-score revealed superior performance in non-invasive diagnosis compared with previously published miRNA biomarkers. Conclusions: We developed and validated a novel and robust blood-based miRNA signature, which may serve as a promising clinically applicable non-invasive tool for the early detection of PE.
2022-09-21 | GSE206988 | GEO
Project description:Hirschsprung disease (HD) is a congenital intestinal anomaly, which derives from a failure to form enteric ganglia in the lower bowel. Surgery is a major therapeutic strategy and neural stem cells transplantation is believed as a promising approach. However, we still face many challenges. To better characterize the pathology of HD, we used Agilent microarrays to analyze the gene expression profiles of surgically resected bowel tissue from 8 HD patients and 8 controls. A total of 253 genes were differentially expressed between the two groups using SAM software with threshold set at fold-change >2.0 and q-value <0.05. Gene Ontology analysis demonstrated that genes related to regulation of neuron development were significantly enriched. Differentially expressed genes (DEGs) involved in neuron development were further validated by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Moreover, in an attempt to seek potential drugs for HD, we correlated the observed gene expression patterns in HD to those of small molecule compounds via the Connectivity Map (cMap) database. Several compounds were screened that could rescue the dysregulated molecular signature in HD, proposing a testable hypothesis about possible therapeutic agents as a novel remedy for HD. In conclusion, our work may enhance our understanding the molecular changes in HD. More importantly, this study opens new fields of investigation into pharmacological intervention for HD.
2018-06-01 | GSE98502 | GEO
Project description:ABSTRACT: Enhancers are important regulators of gene expression in eukaryotes; however, only a few enhancers have been identified in plants, and the genome-wide identifications are lacking. To investigate enhancers in Arabidopsis thaliana, we analyzed the chromatin landscape, RNA Pol II occupancy, and the polyadenylated and non-polyadenylated Arabidopsis transcriptomes, using exosome-deficient lines to capture stable and unstable transcripts. Here we identified the set of unique >1900 regions, termed Putative Enhancers (PEs), carrying canonical chromatin signatures of metazoan transcriptional enhancers. Almost of PEs are intra-genic and transcriptionally active. Unexpectedly, most of the PE carrying these signatures are associated with the 3′ ends of protein-coding genes, enriched in transcription factor binding, with binding motifs resembling polyadenylation signals, thus linking links two hubs of very different, functionally and mechanistically distinct processes – cleavage/polyadenylation and transcription termination of protein-coding genes with transcriptional activation/regulation of different genes. And may present a novel DNA elements with regulatory potential. Additionally, according to high resolution Arabidopsis Hi-C data 24% of identified PEs interact with other protein-coding genes intrachromosomally, through binding by the same set of transcription factors, supporting the notion of co-regulation of expression between PEs and their targets. We also confirmed that PEs are highly conserved in the recently sequenced 1035 different Arabidopsis accessions.
2019-08-20 | GSE99406 | GEO
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:Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. The burden of disease lies mainly in low-middle income countries. The aim of this project is to establish a pre-eclampsia biobank in South Africa to facilitate research in the field of pre-eclampsia with a focus on phenotyping severe disease.The approach of our biobank is to collect biological specimens, detailed clinical data, tests, and biophysical examinations, including magnetic resonance imaging (MRI) of the brain, MRI of the heart, transcranial Doppler, echocardiography, and cognitive function tests.Women diagnosed with pre-eclampsia and normotensive controls are enrolled in the biobank at admission to Tygerberg University Hospital (Cape Town, South Africa). Biological samples and clinical data are collected at inclusion/delivery and during the hospital stay. Special investigations as per above are performed in a subset of women. After two months, women are followed up by telephonic interviews. This project aims to establish a biobank and database for severe organ complications of pre-eclampsia in a low-middle income country where the incidence of pre-eclampsia with organ complications is high. The study integrates different methods to investigate pre-eclampsia, focusing on improved understanding of pathophysiology, prediction of organ complications, and potentially future drug evaluation and discovery.
| S-EPMC8074755 | biostudies-literature
Project description:Prime editing is a highly versatile CRISPR-based genome editing technology with the potential to correct the vast majority of genetic defects1. However, correction of a disease phenotype in vivo in somatic tissues has not been achieved yet. Here, we establish proof-of-concept for in vivo prime editing, that resulted in rescue of a metabolic liver disease. We first develop a size-reduced prime editor (PE) lacking the RNaseH domain of the reverse transcriptase (SpCas9-PERnH), and a linker- and NLS-optimized intein-split PE construct (SpCas9-PE p.1153) for delivery by adeno-associated viruses (AAV). Systemic dual AAV-mediated delivery of this variant in neonatal mice enables installation of a transversion mutation at the Dnmt1 locus with 15% efficiency on average. Next, we targeted the disease-causing mutation in the phenylalanine hydroxylase (Pah)enu2 mouse model for phenylketonuria (PKU). Correction rates of 1.5% using the dual AAV approach could be increased to up to 14% by delivery of full-length SpCas9-PE via adenoviral vector 5 (AdV5), leading to full restoration of physiological blood phenylalanine (L-Phe) levels below 120 µmol/L. Our study demonstrates in vivo prime editing in the liver at two independent loci, emphasizing the potential of PEs for future therapeutic applications.
2021-12-29 | GSE174757 | GEO
Project description:The etiology of preeclampsia, a hypertensive disorder of human pregnancy, remains unknown. We addressed fetal sex selection and the suggestive role of fetal HLA-G and related genes, regulating maternal immune responses, in preeclampsia pathogenesis. We assessed birth sex ratios, weights, and seasonality of preeclampsia among 1.79 million births in Finland. We studied haplotypes of HLA-G 3’ untranslated region (UTR), regulating HLA-G expression, in 1000 Genomes series and in a preeclampsia cohort (n=1249). We quantified placental (n=163) mRNA expression of 136 genes, studied HLA-G and IFNα protein expression by immunohistochemistry, and measured maternal and fetal circulating IFNα levels by ELISA. Population-level data showed loss of male fetuses as a characteristic of preeclampsia. As a potential contributor to immune-mediated loss, we found balancing selection at HLA-G 3’UTR modulating sex ratio, and association of HLA-G 3’UTR haplotypes with placental HLA-G expression. HLA-G and its receptors were downregulated in preeclampsia placentas, and surprisingly, interferon alpha-1 (IFNA1) was highly upregulated. IFNA1 and HLA-G distinguished preeclampsia better than placental FLT1 expression. Fetal but not maternal circulating IFNα, produced by trophoblasts, showed association with maternal hypertension and fetal growth restriction. We uncover the link between placental HLA-G expression and human birth sex ratio. We propose that preeclampsia shares, through reduced HLA-G mediated immunotolerance, the mechanism needed to fight placental viral infections and malaria in evolution. IFNα upregulation in preeclampsia placenta, together with its known actions upstream of inflammatory genes, encourages testing IFNα inhibitors and especially the pregnancy-approved antimalarial hydroxichloroquine in treatment of preeclampsia.
2019-11-25 | GSE125460 | GEO
Project description:modENCODE_submission_3157 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP87 (official name : OP87 genotype : unc-119(ed3) III; wgIs87 [unc-119(+) pes-1::TY1::EGFP::3xFLAG] outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The PES-1::EGFP fusion protein is expressed in the correct pes-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the PES-1 transcription factor. made_by : R. Waterston ); Developmental Stage: L4; Genotype: unc-119(ed3) III; wgIs87 [unc-119(+) pes-1::TY1::EGFP::3xFLAG]; Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage L4; Target gene pes-1; Strain OP87 (official name : OP87 genotype : unc-119(ed3) III; wgIs87 [unc-119(+) pes-1::TY1::EGFP::3xFLAG] outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The PES-1::EGFP fusion protein is expressed in the correct pes-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the PES-1 transcription factor. made_by : R. Waterston ); temp (temperature) 20 degree celsius
2011-03-31 | E-GEOD-26152 | biostudies-arrayexpress