Transcriptional characterization of primary human HLA-G+ extravillous trophoblasts (EVT) and Villous trophoblasts (VT)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Tamara Tilburgs
PROVIDER: E-MTAB-3217 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Transcriptional profiling comparison of human primary villous trophoblast and extra-villous trophoblast (VT and EVT respectively) cells, isolated from the placenta at 8 to 12 weeks gestation, with complimentary transcriptional profiling of choriocarcinoma cell lines JEG-3 and JAR. Based on phenotypic markers, JEG is frequently used as a model for EVT and JAR is used as a model for VT.
2011-04-28 | E-MTAB-429 | biostudies-arrayexpress
Project description:Six patients with seasonal allergic rhinitis were challenged daily for 8 days with birch pollen extract. A mucosal biopsy was obtained from one nostril at basline (day 0) and from the other nostril after allergen challenge (day 9). The mucosal biopsies were digested into single cells, and then sorted into CD4 T cells and CD45+HLA-DR+ cells. Total RNA was extracted, amplified using whole transcriptome amplification, and gene expression was profiled on microarrays. The study design consisted of 6 subjects, 2 cell types (CD4 T cells, CD45+ HLA-DR+ cells), and 2 conditions (baseline, allergen challenge).
2015-09-01 | E-GEOD-49782 | biostudies-arrayexpress
Project description:An allorecognition system depending on interactions between uterine Natural Killer (uNK) cells and placental extravillous trophoblast (EVT) during early pregnancy influences reproductive outcomes in humans. Our previous immunogenetic studies show that particular combinations of maternal Killer Immunoglobulin-like Receptors (KIR) in uNK cells with fetal HLA-C variants on EVT are associated with disorders of pregnancy, especially pre-eclampsia. To identify responses stimulated in uNK cells specifically when activating KIR (KIR2DS1) binds to C2+HLA-C, a combination protective against pre-eclampsia, we modelled KIR-HLA interactions by co-culturing uNK cells with the 721.221 HLA-null cell line transfected to express either C1+ or C2+HLA-C molecules, followed by transcriptome profiling by RNA sequencing. We detect the secretion of key cytokines by uNK cells under the protective combination between KIR2DS1 and C2+HLA-C.
2024-01-10 | E-MTAB-13379 | biostudies-arrayexpress
Project description:HLA-C arose during evolution of pregnancy in the Great Apes 10-15 million years ago. It has a dual function on placental extravillous trophoblasts (EVT) as it contributes to both tolerance and immunity at the maternal-fetal interface. The mode of its regulation is of considerable interest in connection with the biology of pregnancy and pregnancy abnormalities. First trimester primary EVT in which HLA-C is highly expressed, as well as JEG3, an EVT model cell lines, were employed. Single cell RNA-seq data and quantitative PCR identified high expression of the transcription factor ELF3 in those cells. ChIP-PCR confirmed that both ELF3 and MED1 bound to the proximal HLA-C promoter region. However, binding of RFX5 to this region was absent or severely reduced and the adjacent HLA-B locus remained closed. Expression of HLA-C was inhibited by ELF3 siRNAs and by wrenchnolol treatment. Wrenchnolol is a cell-permeable synthetic organic molecule that mimics ELF3 and is relatively specific for binding to ELF3’s coactivator, MED23, as our data also showed in JEG3. Moreover, the ELF3 gene is regulated by a super-enhancer that spans more than 5 Mb, identified by ATAC-seq, as well as by its sensitivity to (+)-JQ1 (inhibitor of BRD4). ELF3 bound to its own promoter, thus creating an autoregulatory feedback loop that establishes expression of ELF3 and HLA-C in trophoblasts. Wrenchnolol blocked binding of MED23 to ELF3, thus disrupting the positive feedback loop that drives ELF3 expression, with down regulation of HLA-C expression as a consequence.
2021-01-27 | GSE165511 | GEO
Project description:The distinct Class I MHC expression pattern in extravillous trophoblasts (EVT) endows them with immune-tolerant properties that enable successful pregnancy. Notwithstanding, it remains elusive how this process is elaborately regulated. Previously, we identified ELF3 as a transcription factor that governs high level HLA-C expression in EVT. In this study, we found that ELF3 also binds to the enhancer region of two NLR genes, NLRP2 and NLRP7, transactivating NLRP7 expression while suppressing expression of NLRP2. We confirmed that NLRP2 suppresses HLA-C expression while in this study we described a novel role for NLRP7 promoting HLA-C expression in trophoblasts. These two NLR genes, highly expressed in trophoblasts, are thus fine-tuned by ELF3 and enable proper expression of HLA-C in trophoblasts.
2023-09-05 | GSE241792 | GEO
Project description:Invasive extravillous trophoblasts (EVTs) of the human placenta are critically involved in successful pregnancy outcome since they remodel the uterine spiral arteries to increase blood flow and oxygen delivery to the placenta and the developing fetus. To gain more insights into their biological role different primary cell culture models are commonly utilised. However, access to early placental tissue may be limited and primary trophoblasts rapidly cease proliferation in vitro impairing genetic manipulation. Hence, trophoblastic cell lines have been widely used as surrogates to study EVT function. Although the cell lines share some molecular marker expression with their primary counterpart, it is unknown to what extent they recapture the invasive phenotype of EVT. Therefore, we here report the first thorough GeneChip analyses of SGHPL-5, HTR-8/SVneo, BeWo, JEG-3 and the novel ACH-3P trophoblast cells in comparison to previously analysed primary villous cytrophoblasts and extravillous trophoblasts. To identify EVT-specific gene expression signatures in trophoblast cell lines, we calcuted differentially expressed genes between pre-defined groups based on the distinct origins of the five trophoblast cell lines under investigation. Comparison 1 comprised EVT, HTR-8/Svneo and SGHPL-5 vs choriocarcinoma cells (ACH-3P, BeWo, JEG-3). Comparison 2 comprised EVT, ACH-3P, BeWo, JEG-3 vs extravillous trophoblast cell lines (HTR-8/SVneo, SGHPL-5).
2010-09-23 | E-GEOD-20510 | biostudies-arrayexpress
Project description:Abnormalities at any stage of trophoblast development may result in pregnancy-related com-plications. Many of these adverse outcomes are discovered later in pregnancy, but the underly-ing pathomechanisms constitute during the first trimester. Acquiring developmentally relevant material to elucidate the disease mechanisms is difficult. Human pluripotent stem cell (hPSC) technology can provide a renewable source of relevant cells. BMP4, A83-01, and PD173074 (BAP) treatment drives trophoblast commitment of hPSCs towards syncytiotrophoblast (STB) but lacks extravillous trophoblast (EVT) cells. EVTs mediate key functions during placentation, remodel-ing of uterine spiral arteries, and maintenance of immunological tolerance. We optimized the protocol for more efficient generation of HLA-Gpos EVT-like trophoblasts from primed hiPSCs. Increasing the concentrations of A83-01 and PD173074, while decreasing bulk cell density re-sulted in the increase of HLA-G of up to 71%. Gene expression profiling support the advance-ments of our treatment regarding the generation of trophoblast cells. The reported differentia-tion protocol will allow the on-demand access to human trophoblast cells enriched for HLA-Gpos EVT-like cells, allowing the elucidation of placenta-related disorders and to investigate the im-munological tolerance towards the fetus, overcoming the difficulties in obtaining primary EVTs without the need for a complex differentiation pathway via naïve pluripotent or trophoblast stem cells.
2023-09-14 | GSE234949 | GEO
Project description:Zika virus (ZIKV) infection at the maternal-placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be differentiated into early gestation syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT). TSCs and STs, but not EVTs, were highly permissive to productive infection with ZIKV strain DAK AR 41524. The impact of ZIKV on the cellular transcriptome showed that infection of TSCs and STs increased expression of immune related genes, including those involved in type I and type III interferon responses. ZIKV exposure altered extracellular vesicle (EV) protein, mRNA, and miRNA cargo, regardless of productive infection. These findings suggest that early gestation macaque TSCs and STs are permissive to ZIKV infection, and that EV analysis may provide a foundation for identifying non-invasive biomarkers of placental infection in a highly translational model.
2022-05-20 | PXD033289 | Pride
Project description:Three types of HLA-G+ EVT were purified from placental tissues. To investigate transcriptional differences RNA was isolated and gene expression profiles were generated by employing Affymetrix HG_U133_Plus 2 arrays on the Affymetrix Geneatlas system.
2020-06-16 | E-MTAB-8639 | biostudies-arrayexpress
Project description:Invasion of cytotrophoblasts into uterine tissues is essential for placental development. To identify molecules regulating trophoblast invasion, mRNA signatures of purified villous (CTB, poor invasiveness) and extravillous (EVT, high invasiveness) trophoblasts isolated from first trimester human placentae and villous explant cultures, respectively, were compared using GeneChip analyses yielding 991 invasion/migration related transcripts. Several genes involved in physiological and pathologic cell invasion, including ADAM-12,-19,-28 as well as Spondin-2, were upregulated in EVT. Pathway prediction analyses identified several functional modules associated with either the invasive or the non-invasive trophoblast phenotype. One of the genes which were downregulated in the invasive mRNA pool, heme oxygenase-1 (HO-1), was selected for functional analyses. Real-time PCR analyses, Western blottting, and immunofluorescene of first trimester placentae and differentiating villous explant cultures demonstrated downregulation of HO-1 in invasive EVT as compared to CTB. Modulation of HO-1 expression in loss-of as well as gain-of function cell models (BeWo and HTR8/SVneo, respectively) demonstrated an inverse relationship of HO-1 expression with trophoblast migration in transwell and wound healing assays. Importantly, HO-1 expression led to an increase in protein levels and activity of the nuclear hormone receptor PPARgamma. Pharmacological inhibition of PPARgamma abrogated the inhibitory effects of HO-1 on trophoblast migration. Collectively, our results demonstrate that gene expression profiling of EVT and CTB can be used to unravel novel regulators of cell invasion. Accordingly, we identify heme oxygenase-1 as a negative regulator of trophoblast motility acting via upregulation of PPARgamma. Experiment Overall Design: To identify genes potentially regulating cell invasion trophoblast cells of early human gestation with distinct invasive properties were profiled. Experiment Overall Design: Distinct gene expression signatures of highly invasive EVT (n = 6) and poorly invasive CTB (n = 5) of different first trimester placentae using Affymetrix U133A GeneChips interrogating >20,000 genes were determined.
2009-01-30 | E-GEOD-9773 | biostudies-arrayexpress