Ontology highlight
ABSTRACT:
PROVIDER: PRJNA808440 | ENA |
REPOSITORIES: ENA
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Project description:Implantation is the attachment of embryo in the endometrium. Failure in implantation is a major cause of early pregnancy loss. During implantation, the temporal uterine lumen closure can help embryo attach to the uterus. In pigs, extending of endometrial folds to form interlocking finger-like projections is a main cause leads to uterine lumen closure during attachment time, but the underlying mechanisms are largely unknown. Our data reveal that pig uterine luminal epithelium (LE) migrate in coordinated groups during extending of endometrial folds. Moreover, the MALDI-TOF MS based N-glycomic characterization of porcine endometrium revealed α2,6-linked sialic acid are highly expressed in pig uterine LE during extending of endometrial folds. To investigated the mechanisms by which α2,6-sialylated proteins in formation of the endometrial folding during implantation in pigs, the α2,6-sialylated proteins in pig uterine LE were characterized by proteomic analysis and those proteins that are involved in cell adhesion, such as E-cadherin, were detected. Finally, our in vivo and in vitro data show that α2,6-sialylation of E-cadherin occurs in accompany with collective epithelial migration. The results provide new insight into the mechanism of pig implantation by identifying that α2,6-sialylation of cell adhesion molecules may participate in formation of extending of endometrial folds through promoting of collective migration of uterine LE.
2022-02-17 | PXD027571 | Pride
Project description:Recon 2M.2 is a generic genome-scale metabolic model of Homo sapiens, in which a framework for gene-transcript-protein-reaction associations (GeTPRA) was deployed to generate metabolic reactions by considering the effects of alternative splicing of metabolic genes (i.e., both principal and non-principal transcripts). Eight versions of COBRA-compliant SBML files are available for Recon 2M.2 depending on the use of: MNXref versus BiGG IDs (metabolite IDs); Entrez gene IDs (GPR associations) versus Ensembl transcript IDs versus RefSeq transcript IDs versus UCSC transcript IDs (TPR associations for the last three database IDs).
2022-05-16 | MODEL2205110002 | BioModels
Project description:The protein encoded by this gene is an axonal glycoprotein belonging to the immunoglobulin supergene family. The ectodomain, consisting of several immunoglobulin-like domains and fibronectin-like repeats (type III), is linked via a single transmembrane sequence to a conserved cytoplasmic domain. This cell adhesion molecule plays an important role in nervous system development, including neuronal migration and differentiation. Mutations in the gene cause X-linked neurological syndromes known as CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus). Alternative splicing of this gene results in multiple transcript variants, some of which include an alternate exon that is considered to be specific to neurons.
2016-09-01 | GSE86268 | GEO
Project description:Study question : Are there changes in transcript levels as endometrial receptivity changes in patients with recurrent implantation failure (RIF), particularly in alternative splicing events (ASEs), differential expression genes (DEGs) and immune cells levels? Summary answer: Changes in endometrial receptivity affect alternative splicing (AS), differential gene expression and immune cells, and the RNA-binding protein (RBP) KHDRBS3 likelymaybe？ Likely？ is involved in the dysregulation of alternative splicing. What is known already: Endometrial receptivity is critical for RIF patients. Researchers have developed transcript level-based models to predict personalized endometrial assessment at WOI. Investigating alternative splicing dysregulation, immune cells and other transcriptional biomarkers in RIF patients may further help to predict endometrial receptivity and improve embryo implantation success. Study design, size, duration: 90 endometrial samples were collected from fertile healthy controls (HC) during the menstrual cycle, including pre-receptive (PR) (luteinising hormone (LH)+3 days/LH+5 days), receptive (R) (LH+7 days) and post-receptive (PS) (LH+9 days) phases. 73 endometrial samples were taken from RIF patients on hormone replacement therapy (HRT) cycles, including PR (progesterone (P)+3 days), R (P+5 days) and PS (P+7 days) phases. Participants/materials, setting, methods: Total RNA was extracted and sequenced for all 163 endometrial samples . Bioinformatic analysis was used to comprehensively investigate the endometrial transcriptome at different stages of receptivity. We elucidated the biological significance of the universal alteration of alternative splicing in endometrial receptivity and further analyzed the role of immune cells and gene expression in this process. In addition, an ASEs-RBPs correlation network was constructed in the endometrial receptive period to evaluate the dysregulation of AS by RBPs. Main results and the role of chance: Global splicing profiling of the four subgroups (HC: PR vs. R; HC: PS vs. R; RIF: PR vs. R; RIF: PS vs. R) consistently showed that skipped exons (SE) and mutually exclusive exons (MXE) were the most common changes in splicing events. These different ASEs occurred at high frequency and some of them could affect the coding potential of a transcript. A greater number of genes with different alternative splicing events (ASEGs) were identified between PR and R phases than between PS and R phases, and the same trend was observed for differentially expressed genes (DEGs). Both ASEGs and DEGs showed enrichment for pathways associated with cell function and adhesion, while DEGs were also enriched for cytokine and immune-related pathways. Immune cell prediction shows that changes in endometrial receptivity phases result in differences in the levels of CD8 T cells, resting NK cells and other immune cells. During the R phase, there was a significant decrease in CD8 T cells and resting NK cells, whereas monocytes and M0 macrophages were significantly increased compared to the endometrial PR phase in RIF patients. Similarly, analysis of immune cells showed a significant increase in CD8 T cells, M1 and M2 macrophages and a significant decrease in activated NK cells in the R phase compared to the PS phase of the endometrium in RIF patients. Some of these immune cells, such as NK cells and monocytes, are highly correlated with certain ASEs. Investigation of ASEs-RBPs networks suggested that KHDRBS3 may be a key regulator of splicing events. Limitations, reasons for caution: The sample size needs to be increased and cover a variety of situations, such as different age, pathology, dietary habits, etc., and alsothe molecular experimental validation needs to be considered. The lack of direct comparisons between natural and HRT cycles in the same sample and molecular experimental validation need to be considered. Wider implications of the findings: Comprehensive transcriptional analysis of the endometrium provide valuable insight into potential biomarkers related to endometrial receptivity and potential treatments for RIF patients. Study funding/competing interest(s): This study was supported by Supported by the Program of National Natural Science of China (Grant No. 81701409). All authors declared that they have no conflicts of interest.
2025-10-15 | GSE287072 | GEO
Project description:RNA-binding proteins and their mediated alternative splicing play important roles in tumor cell invasion and migration. Here, we report that ESRP1 is a key regulator of gastric cancer cell metastasis. Overexpression of ESRP1 inhibits the invasion and migration of gastric cancer cells, in vivo and in vitro. Furthermore, we found that ESRP1 causes a wide range of alternative splicing events, and ESRP1-mediated CLSTN1 exon skipping may be a key mechanism for its inhibition of gastric cancer cell invasion and metastasis. Taken together, our data provide a molecular framework for the role of ESRP1 in gastric cancer development.
2023-12-27 | GSE233685 | GEO
Project description:The endometrium contains a distinct population of immune cells consisting of 70% natural killer (NK) cells that undergo cyclic changes during the menstrual cycle. However, how these uterine NK (uNK) cells interact with uterine stromal cells (SC) remains unclear. We therefore investigated the paracrine effect of medium conditioned by uNK cells on the gene expression profile of endometrial SC in-vitro using a cDNA Microarray. Our results, verified by real-time PCR and ELISA, reveal that soluble factors from uNK cells substantially alter endometrial SC gene expression. The largest group of up-regulated genes found were chemokines and cytokines, including IL-15 and IL-15Rα. The latter could produce a niche for uNK cells allowing proliferation within and recruitment into the uterus, as seen in bone marrow. In addition, the most abundantly up-regulated genes, including IL-8, CCL8 and CXCL1 have also been shown to be stimulated by contact of SC with trophoblast, suggesting that uNK cells work synergistically to support the initial trophoblast migration during implantation. Overall this study demonstrates for the first time the paracrine communication between uNK cells and uterine SC, and adds to the understanding of how the uterine immune system contributes to the changes seen within the cycling endometrium. Keywords: Response of endometrial stromal cells to uNK conditioned medium
2009-01-31 | GSE9718 | GEO
Project description:Repair after damage is essential for tissue homeostasis. Post-menstrual repair of the uterine endometrium is a unique cyclical manifestation of rapid, scar-free, tissue repair taking ~3-5 days. Skin repair post-wounding is slower (~2 weeks) and, in the case of chronic wounds, takes months/years to restore integrity. Herein, the unique ‘rapid-repair’ endometrial environment is translated to the ‘slower-repair’ skin environment. Menstrual fluid (MF), the milieu of post-menstrual endometrial repair, facilitates healing of endometrial and keratinocyte ‘wounds’ in vitro, promoting cellular adhesion and migration, stimulates keratinocyte migration in an ex vivo human skin-reconstruct model and promotes re-epithelialization in an in vivo porcine wound model. Proteomic analysis of MF identified a large number of proteins; several proteins were selected for further investigation, with the endometrium demonstrated as the source of these factors. Functionally, they promote repair of endometrial and keratinocyte wounds by promoting migration, differing significantly from currently available wound-repair treatments, which mainly promote proliferation. Development of these and other menstrual fluid factors into a ‘migration-inducing’ treatment paradigm will provide novel therapies for tissue repair.
2018-07-30 | PXD007234 | Pride
Project description:Epigenetic silencing of Steroidogenic Factor 1 (SF1) is lost in endometrial tissue in endometriosis and this is hypothesized to result in de novo local steroidogenesis favoring growth and inflammation. The goal of this study was to evaluate the endometrial specific transcriptional and functional role of SF1 in vivo by utilizing a mouse model in which SF1 was conditionally expressed in the uterus. SF1 expression resulted in the development of cystic endometrial glands and infertility. Endometriosis induction by auto-transplantation of a biopsy of uterine tissue sutured to the mesenteric membrane resulted in 4-fold increase in size ectopic lesions from SF1 expressing mice. Microarray analysis demonstrated SF1-regulated genes are involved in several pathways including epithelial and tube development, migration of lymphocytes and leukocytes, cellular movement and vascular development. experimental group (SF-1 transgenic) and control group
2016-04-14 | E-GEOD-66963 | biostudies-arrayexpress
Project description:The endometrium contains a distinct population of immune cells consisting of 70% natural killer (NK) cells that undergo cyclic changes during the menstrual cycle. However, how these uterine NK (uNK) cells interact with uterine stromal cells (SC) remains unclear. We therefore investigated the paracrine effect of medium conditioned by uNK cells on the gene expression profile of endometrial SC in-vitro using a cDNA Microarray. Our results, verified by real-time PCR and ELISA, reveal that soluble factors from uNK cells substantially alter endometrial SC gene expression. The largest group of up-regulated genes found were chemokines and cytokines, including IL-15 and IL-15Rα. The latter could produce a niche for uNK cells allowing proliferation within and recruitment into the uterus, as seen in bone marrow. In addition, the most abundantly up-regulated genes, including IL-8, CCL8 and CXCL1 have also been shown to be stimulated by contact of SC with trophoblast, suggesting that uNK cells work synergistically to support the initial trophoblast migration during implantation. Overall this study demonstrates for the first time the paracrine communication between uNK cells and uterine SC, and adds to the understanding of how the uterine immune system contributes to the changes seen within the cycling endometrium. Keywords: Response of endometrial stromal cells to uNK conditioned medium This study was designed to identify the response of non-decidualised stromal cells from the endometrium, to soluble factors secreted by uterine NK cells. Endometrial stromal cells were isolated from 7 patients and treated with control medium or medium conditioned by uterine Nk cells. THE 'REF' COLUMN ON EACH ARRAY IS THE SIGNAL PRODUCED BY A COMMON REFERNCE RNA SAMPLE THAT WAS LABELLED AS A SINGLE BATCH SAMPLE AND HYBRIDISED TO ALL THE ARRAYS- IT IS A 'COMMON REFERENCE'. THE 'TEST' SAMPLE COMPRISES EACH INDIVIDUAL SAMPLE OF CELLS TREATED AS DESCRIBED IN THE SERIES SUBMISSION. FOR EXAMPLE; SAMPLE Y1 (gsm2435820) IS RNA FROM PATIENT 1 TREATED WITH CONTROL MEDIUM, SAMPLE G1 (GSM245371) IS RNA FROM PATIENT 1 TREATED WITH NK CONDITIONED MEDIUM THESE TWO SAMPLES THEREFORE FORM A PAIR- IE CELLS FROM THE SAME PATIENT TREATED WITH CONTROL OR NK-CONDITIONED MIDIUM. Y2,G2 ARE FROM PATIENT 2, ETC
2010-06-24 | E-GEOD-9718 | biostudies-arrayexpress