Placental Accreta Spectrum: Upregulated Cytotrophoblast DOCK4 Contributes to Over Invasion
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PROVIDER: PRJNA561109 | ENA |
REPOSITORIES: ENA
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Project description:In humans, a subset of placental cytotrophoblasts (CTBs) invades the uterus and its vasculature, anchoring the pregnancy and ensuring adequate blood flow to the fetus. Appropriate depth is critical. Shallow invasion increases the risk of pregnancy complications, e.g., severe preeclampsia. Overly deep invasion, the hallmark of placenta accreta spectrum (PAS), increases the risk of pre-term delivery, hemorrhage and death. Previously a rare condition, the incidence of PAS has increased to 1:731 pregnancies, likely due to the rise in uterine surgeries (e.g., Cesarean sections). CTBs track along the scars deep into the myometrium and beyond. Here we compared the global gene expression patterns of CTBs from PAS cases to gestational age-matched control cells that invaded to the normal depth from preterm birth (PTB) deliveries. The mRNA encoding the guanine nucleotide exchange factor, DOCK4, mutations of which promote cancer cell invasion and angiogenesis, was the most highly differentially expressed molecule in PAS samples. Over-expression of DOCK4 increased CTB invasiveness, consistent with the PAS phenotype. Also, this analysis identified other genes with significantly altered expression in this disorder, potential biomarkers. These data suggest that CTBs from PAS cases up regulate a cancer-like pro-invasion mechanism, suggesting molecular as well as phenotypic similarities in the two pathologies.
2019-09-30 | GSE136048 | GEO
Project description:In humans, a subset of placental cytotrophoblasts (CTBs) invades the uterus and its vasculature, anchoring the pregnancy and ensuring adequate blood flow to the fetus. Appropriate depth is critical. Shallow invasion increases the risk of pregnancy complications, e.g., severe preeclampsia. Overly deep invasion, the hallmark of placenta accreta spectrum (PAS), increases the risk of preterm delivery, hemorrhage, and death. Previously a rare condition, the incidence of PAS has increased to 1:731 pregnancies, likely due to the rise in uterine surgeries (e.g., Cesarean sections). CTBs track along scars deep into the myometrium and beyond. Here we compared the global gene expression patterns of CTBs from PAS cases to gestational age-matched control cells that invaded to the normal depth from preterm birth (PTB) deliveries. The messenger RNA (mRNA) encoding the guanine nucleotide exchange factor, DOCK4, mutations of which promote cancer cell invasion and angiogenesis, was the most highly up-regulated molecule in PAS samples. Overexpression of DOCK4 increased CTB invasiveness, consistent with the PAS phenotype. Also, this analysis identified other genes with significantly altered expression in this disorder, potential biomarkers. These data suggest that CTBs from PAS cases up-regulate a cancer-like proinvasion mechanism, suggesting molecular as well as phenotypic similarities in the two pathologies.
| S-EPMC7355036 | biostudies-literature
Project description:Human cytotrophoblast organoid cultures were established from the villous trophoblast of first trimester placentas. We analyzed the global expression profile of the cytotrophoblast organoids (CTB-ORG) and compared to the profile of the tissue of origin i.e. villous cytotrophoblast (vCTB) as well as to differentiated syncytiotrophoblast (STB) and placental fibroblasts (FIB).
2018-08-02 | GSE109976 | GEO
Project description:To find potential biomarkers and molecular mechanism for placenta accreta spectrum disorders , we identified the differently expressed patterns of lncRNAs and mRNAs in invasive placneta and adherent normal placenta tissues. The results provided a novel insight into the pathogenesis of placenta accreta spectrum disorders .
2020-02-14 | GSE126552 | GEO
Project description:Placenta accreta is a major cause of maternal morbidity and mortality in modern obstetrics. The study aims to identify the differently expressed lncRNA and mRNA in placenta accreta patients compared with controls and to determine biological pathways, which provides a novel insight ingto thepathogenesis of placneta accreta.
2021-12-29 | GSE148952 | GEO
Project description:Transcriptome analysis of FFPE placenta of placenta accreta spectrum, over increta. Pre-diagnosis is essential to safely deal with placenta accrete spectrum, but definitive diagnostic markers have not yet been established. We conducted a transcriptome analysis of FFPE placenta to establish early diagnostic markers for placenta accreta.
2023-11-01 | GSE189267 | GEO
Project description:Embryonic and extraembryonic development quickly diverges. Other than a globally hypomethylated genome, little is known about the epigenetic changes of placental cells throughout gestation. We profiled DNA methylation and activating/repressing histone modifications of cytotrophoblasts and four extraembryonic compartments in 2nd trimester and at term. Unexpectedly, in cytotrophoblasts, H3K9me3 occupancy precisely overlapped domains with more pronounced DNA hypomethylation and repressed transcription. At term, immunoblotting and -localization revealed extensive depletion of this and other histone modifications that paralleled increased genome-wide DNA methylation, which included hundreds of promoters. Candidate enhancers within embryonic stem cell differentially methylated regions (DMRs) revealed pluripotency factors, while those within cytotrophoblast DMRs revealed transcription factor binding motifs and genes that regulate placental development. DNA methylation, RNA, and miRNA profiling of the extraembryonic compartments identified regional specializations and gestational age regulation. Cytotrophoblast mRNAs that were down-regulated at term were enriched for genes up-regulated in severe preeclampsia. Correspondingly, immunoanalyses of cytotrophoblast histone modifications showed strong H3K27ac upregulation in severe preeclampsia. Thus, as gestation proceeded, certain cytotrophoblast histone modifications declined precipitously while, in pregnancy complications, these normal patterns were markedly perturbed. These data suggested an unusual genome-scale pattern of alterations in the abundance of histone modifications over the lifetime of the placenta. Marked alterations in this pattern were associated with pregnancy complications, indicating a possible causative role.
2017-05-17 | GSE98938 | GEO
Project description:Objective: The objective of this study is to utilize advances in single-cell RNAsequencing to characterize cellular heterogeneity and transcriptomic signatures of PAS. Our findings can elucidate mechanisms of abnormal placental invasion and identify targets for potential diagnostic and therapeutic biomarkers of PAS. Results: Placental samples from PAS participants and non-PAS cesarean births were included. In total, we analyzed 31,406 individual cells expressing an average of 1,493 genes. Clustering analysis of gene expression identified multiple populations of cells representing syncytiotrophoblasts, cytotrophoblasts, extravillous trophoblasts, decidua,endothelial cells, myeloid, natural killer, and lymphoid cells. When analyzed by disease phenotype, AI showed a unique gene signature most prominently in the endothelial population. The highest expression in AI compared to AO and C was seen in the following genes: DLK1, EGFL6, HGF, APOLD1, and EDNRB. Gene set enrichment analysis of AI endothelial cells identified the following key pathways: blood vessel development, response to growth factors and hormones, regulation of cell adhesion and migration, and pathways in cancer. Conclusions: We present a comprehensive single-cell atlas of PAS across the site of invasion and site of non-adherence. By integrating expression from individual genes per cell, we identified endothelial cells as a key subpopulation in invasive accreta, with expression of genes involved in multiple angiogenic, growth, and mechanical-signaling pathways. After validation, these gene targets may be used to refine diagnostic assays for placenta accreta in early gestation, track disease progression over time, and inform Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation therapeutic discoveries.
2024-02-02 | GSE236675 | GEO
Project description:This study utilizes advances in single-cell RNA-sequencing to generate transcriptomes from placenta accreta and control specimens.
2024-02-05 | GSE212505 | GEO
Project description:RNA sequencing profiling of placental tissues from placenta accreta and control pregnancies
| PRJNA626612 | ENA