The elevated YTHDC1 affects trophoblastic function and induces preterm birth in ART conception via augmenting RPL37 translation
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ABSTRACT:
PROVIDER: PRJNA1022799 | ENA |
REPOSITORIES: ENA
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Project description:Here, it is shown that YTHDC1 was significantly increased in the human preterm placenta after ART and the murine preterm placenta after E2 exposure. Overexpression of YTHDC1 significantly promoted the proliferation, migration, and invasion of trophoblast cells, but inhibited their apoptosis. Knockdown or knockout of YTHDC1 played an opposite effect. Mechanistically, E2 promoted YTHDC1 expression through retinoid X receptor alpha (RXRA) upregulation. YTHDC1 could activate WNT and JAK/STAT signaling pathways in the human trophoblast cells. Meanwhile, YTHDC1 could fine-tone the translation of ribosomal protein L37 (RPL37) in a m6A-dependent manner, which then influence the cellular total protein synthesis. Importantly, administration of siRNA targeting YTHDC1 effectively delays preterm birth in vivo. Collectively, these findings uncover the epigenetic mechanism underlying ART preterm birth and provide a potential target for therapeutic intervention.
2024-09-30 | GSE244402 | GEO
Project description:The human placenta is covered by a single multinucleated fetal cell, the syncytiotrophoblast, which is bathed in maternal blood. During all pregnancies, membrane enclosed extracellular vesicles derived from the syncytiotrophoblast are extruded into the maternal blood.The large size of these extracellular vesicles (diameter larger than 10µm) is referred to as trophoblastic debris in this study. We have shown in the past that endothleial cells are involved in clearence of this trophoblastic debris and induction of immune tolerence by trophoblastic debris.This study aimed to characterise the transcriptional changes that occur in human vascular endothelial cells following exposure to trophoblastic debris from normal first trimester placentae. Microarrays were used to probe transcriptomic changes 2 and 21 hours after exposure of endothelial cells (Human microvascular endothelial cell line,HMEC-1) to trophoblastic debris from normal first trimester placentae
2016-08-21 | GSE69996 | GEO
Project description:The human placenta is covered by a single multinucleated fetal cell, the syncytiotrophoblast, which is bathed in maternal blood. During all pregnancies, membrane enclosed extracellular vesicles derived from the syncytiotrophoblast are extruded into the maternal blood.The large size of these extracellular vesicles (diameter larger than 10µm) is referred to as trophoblastic debris in this study. We have shown in the past that endothleial cells are involved in clearence of this trophoblastic debris and induction of immune tolerence by trophoblastic debris.This study aimed to characterise the transcriptional changes that occur in human vascular endothelial cells following exposure to trophoblastic debris from normal first trimester placentae. Microarrays were used to probe transcriptomic changes 2 and 21 hours after exposure of endothelial cells (Human microvascular endothelial cell line,HMEC-1) to trophoblastic debris from normal first trimester placentae Trophoblastic debris were isolated by low speed centrifugation from three individual first trimester human placentae (three biological replicates). The protein content in trophoblastic debris was measured by BCA assay. HMEC-1 was co-cultured with trophoblastic debris (60ug/ml total debris protein contents) for either 2 or 21 hours before RNA extraction. Untreated HMEC-1 at 2 and 21 hours were used as controls.In total, 12 samples were analyzed.
2016-08-21 | E-GEOD-69996 | biostudies-arrayexpress
Project description:ART is associated with abnormalities in DNA methylation and a higher incidence of adverse pregnancy outcomes in humans and mice. However, which specific exposure, among the interventions utilized during ART, is responsible for these outcomes remains unknown. Embryo transfer after vitrification-thaw (frozen ET) into a maternal hormonal environment more closely resembling unassisted conception is increasingly utilized clinically, but reports suggest a higher incidence of large for gestational age (LGA) infants, with male infants potentially more affected than female infants.
2022-04-26 | GSE201496 | GEO
Project description:Gene expressions obtained from the total RNA sequencing of 2 choriocarcinomas, 4 epithelioid trophoblastic tumors, and 4 placental site trophoblastic tumors were evaluated for differential gene expression, pathway alteration, fusion gene, infiltrating immune cell type, and PD-L1 expression level, and mutation analysis was performed using the RNA sequencing data.
2021-01-04 | GSE135727 | GEO
Project description:Cells have evolved a robust and highly regulated DNA damage response to preserve their genomic integrity. Although increasing evidence highlights the relevance of RNA regulation, our understanding of its impact on a fully efficient DNA damage response remains limited. Here, through a targeted CRISPR-knockout screen, we identified RNA binding proteins and modifiers that participate in mediating the p53 response. Among the top hits, m6A reader YTHDC1 was identified as a master regulator of p53 expression. YTHDC1 binds to the transcription start sites ofTP53and other genes involved in DNA damage response, promoting their transcriptional elongation. YTHDC1 deficiency leads to reducedTP53expression, and also retention of introns leading to aberrant protein production of key DNA damage factors. While intron retention is dependent on m6A, YTHDC1 favoursTP53transcriptionalpause-release independently of m6A. Depletion of YTHDC1 causes genomic instability and aberrant cancer cell proliferation mediated by genes regulated by YTHDC1. Our results uncover YTHDC1 as an orchestrator of the DNA damage response through distinct mechanisms of co-transcriptional mRNA regulation.
2024-05-07 | GSE239331 | GEO
Project description:Label the cells overexpressed Flag tagged YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 and SRSF10 with 4-SU, the RNA bound by YTHDC1 and SRSF proteins can be got by Flag IP followed by RNA isolation by using the TRIzol (Invitrogen) reagent by following the company manual.the RNA was then used for library preparation using a TruSeq⢠RNA Sample Prep Kit v2 (Illumina, San Diego, CA, USA) according to the manufacturerâs protocol.The libraries were sequenced using HiSeq2000 (Illumina) in single-read mode, creating reads with a length of 101 bp. Sequencing chemistry v2 (Illumina) was used and samples were multiplexed in two samples per lane. Discovery of the binding motif of YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 or SRSF10 in overexpressed Human HeLa cells
2016-02-17 | E-GEOD-71096 | biostudies-arrayexpress
Project description:The term gestational trophoblastic disease (GTD) describes a range of pathologies derived from the villous trophoblasts of the placenta. These include benign entities such as partial and complete hydatidiform mole as well as invasive cancers such as gestational choriocarcinoma, placental site trophoblastic tumors, and epithelioid trophoblastic tumors. Collectively, the malignant forms of GTD are known as gestational trophoblastic neoplasia (GTN). The risk of GTN following a complete molar pregnancy ranges between 8-25%. Low risk patients are expected to have a high likelihood of response to single agent chemotherapy with methotrexate or actinomycin D, but the incidence of resistance to single agent chemotherapy among low risk patients remains 25-50%. We used gene expression microarrays to compare methotrexate sensitive trophoblastic cell lines to sublines that were conditioned to become methotrexate resistant.
2017-03-03 | GSE88873 | GEO
Project description:we investigate the role of YTHDC1 in normal hematopoiesis and adult hematopoietic stem/progenitor cell (HSPC) maintenance in vivo. Utilizing conditional Ythdc1 knockout mice ,we show that YTHDC1 is required for hematopoietic stem cell (HSC) maintenance as well as self-renewal of HSC. Transcriptome analysis identified many differentially expressed genes (DEGs) between WT and YTHDC1-KO LT-HSCs.
2023-07-01 | GSE208626 | GEO
Project description:The goal of this study is to identify YTHDC1 binding targets in MOLM13 cells(AML).
2021-05-24 | GSE168568 | GEO