MiRNome of endometriotic lesion
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE56414 | GEO | 2015/01/06
SECONDARY ACCESSION(S): PRJNA243268
REPOSITORIES: GEO
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Project description:The development and progression of endometriotic lesions are poorly understood, but immune cell dysfunction and inflammation are closely associated with the pathophysiology of endometriosis. A lack of suitable 3D in vitro models permitting the study of interactions between cell types and the microenvironment is a contributing factor. To address this limitation, we developed endometriotic organoids (EO) to explore the role of epithelial-stromal interactions and model peritoneal cell invasion associated with lesion development. Using a non-adherent microwell culture system, spherical organoids were generated with endometriotic epithelial cells (12Z) combined with immortalized endometriotic stromal cells (iEc-ESC) or immortalized uterine stromal cells (iHUF). Organoids self-organized with stromal cells occupying the center and epithelial cells on the periphery of the organoid. Endometriotic organoids (EO), containing iEc-ESC, resulted in the development of stratified 12Z epithelial cells compared to those with iHUF where the 12Z cells developed as a single layered epithelium. Transcriptomic analysis found 4,522 differentially expressed genes (DEG) between EO and 12Z/iHUF organoids, and the top DEG included increased expression of interleukins and prostaglandin synthase enzymes. An overlap of the EO DEG with baboon endometriotic lesions was highly significant. Finally, to mimic invasion of endometrial tissue into the peritoneum, a model was developed using EO and extracellular matrix containing human peritoneal mesothelial cells (LP9). Invasion of EO into the extracellular matrix-LP9 layer was increased in presence of estrogen or THP1-derived proinflammatory macrophages. Taken together, our results strongly support the concept that EO are an appropriate model for dissecting mechanisms that contribute to endometriotic lesion development.
2022-06-15 | GSE202661 | GEO
Project description:The mechanisms underlying the pathophysiology of endometriosis, characterized by the presence of endometrium-like tissue outside the uterus, remain poorly understood. This study aimed to identify cell type-specific gene expression changes in superficial peritoneal endometriotic lesions and elucidate the crosstalk among the stroma, epithelium, and macrophages compared to patient-matched eutopic endometrium. Surprisingly, comparison between lesions and eutopic endometrium revealed transcriptional similarities, indicating minimal alterations in the sub-epithelial stroma and epithelium of lesions. Spatial transcriptomics (NanoString GeoMx) highlighted increased signaling between the lesion epithelium and macrophages, emphasizing the role of the epithelium in driving lesion inflammation. We propose that the superficial endometriotic lesion epithelium orchestrates inflammatory signaling and promotes a pro-repair phenotype in macrophages, providing a new role for Complement 3 in lesion pathobiology. This study underscores the significance of considering spatial context and cellular interactions in uncovering mechanisms governing disease in endometriotic lesions.
2024-04-16 | GSE263897 | GEO
Project description:Spatial Transcriptomic Analysis of Superficial Peritoneal Endometriotic Lesions
| PRJNA1099697 | ENA
Project description:To identify specific markers of rectovaginal endometriotic nodule vasculature, highly enriched preparations of vascular endothelial cells and pericytes were obtained from endometriotic nodules and control endometrial and myometrial tissue by laser capture microdissection (LCM), and gene expression profiles were screened by microarray analysis. Of the 18,400 transcripts on the arrays, 734 were significantly overexpressed in vessels from fibromuscular tissue and 923 in vessels from stromal tissue of endometriotic nodules, compared to vessels dissected from control tissues. The most frequently expressed transcripts included known endothelial cell-associated genes, as well as transcripts with little or no previous association with vascular cells. The higher expression in blood vessels was further corroborated by immunohistochemical staining of 6 potential markers, 5 of which showed strong expression in pericytes. The most promising marker was matrix Gla protein, which was found to be present in both glandular epithelial cells and vascular endothelial cells of endometriotic lesions, while it was barely expressed at all in normal endometrium.
2007-09-30 | E-MEXP-1251 | biostudies-arrayexpress
Project description:In this study, we comparatively analyzed the members of the miR-449 family (miR-449a, miR-449b, and miR-449c) with regards to their target genes and functional effects in hepatocellular carcinoma (HCC). Microarray analysis after transient transfection of miR-449a, miR-449b, and/or miR-449c in the HCC cell line HLE identified putative target genes of miR-449a, miR-449b, and miR-449c. For transient overexpression of miRNAs, the HCC cell line HLE was transfected with 50 nM Allstars Negative Control or miScript miRNA mimics. MiRNA mimics for miR-449a, miR-449b, and miR-449c were either single transfected or cotransfected in equimolar amounts (16.7 nM each). Global mRNA expression profiling was performed utilizing pooled RNA of three biological replicates per microarray and two microarrays per condition.
2015-11-06 | E-GEOD-74710 | biostudies-arrayexpress
Project description:Endometriosis is one of the most common causes of chronic pelvic pain and infertility that affects 10% of women of reproductive age. It is currently defined as the presence of endometrial epithelial and stromal cells at ectopic sites; however, advances in endometriosis research have some authors believing that endometriosis should be re-defined as “a fibrotic condition in which endometrial stroma and epithelium can be identified”. microRNAs (miRNAs) are regulatory molecules that potentially play a role in endometriotic lesion development. There is evidence that suggests that miRNAs, including microRNA-21 (miR-21), participate in fibrotic processes in different organs, including the heart, kidney, liver and lungs. The objective of this study was to understand the role of miR-21 and the mechanisms that can contribute to the development of fibrosis by determining how IL-6 regulates miR-21 expression and how this miRNA regulates the transforming growth factor beta (TGF-β) signaling pathway to promote fibrosis. We investigated the expression of miR-21 in the baboon and mouse model of endometriosis and its correlation with fibrosis. We demonstrated that inflammation and fibrosis are present at a very early stage of endometriosis and that the inflammatory environment in the peritoneal cavity, which includes interleukin 6 (IL-6), can regulate the expression of miR-21 in vitro and in vivo.
2024-09-13 | GSE274922 | GEO
Project description:We utilized fluorescence-activated cell sorting to isolate endometrial stromal cells from paired endometrial and endometrioma biopsies and combined it with high-throughput sequencing to determine miRNA alterations in endometriotic stroma. The analysis revealed 149 abnormally expressed miRNAs in endometriotic lesions, including extensive upregulation of miR-139-5p and downregulation of miR-375 compared to eutopic cells. The results of this study provide further insights into the complex molecular mechanisms involved in endometriosis pathogenesis and demonstrate the necessity for cell-type specific analysis of ectopic tissues to understand the interactions between different cell populations in disease onset and progression.
2019-01-15 | GSE121406 | GEO
Project description:The pathophysiology of endometriotic lesion development remains unclear but involves a complex interaction between ectopic endometrium and host peritoneal tissues. We hypothesised that disruption of this interaction was likely to suppress endometriotic lesion formation. We hoped to delineate the molecular and cellular dialogue between ectopic human endometrium and peritoneal tissues in nude mice, as a first step towards testing this hypothesis. Human endometrium was xenografted into nude mice and the resulting lesions were analysed using microarrays. A novel technique was developed that unambiguously determined whether RNA transcripts identified by the microarray analyses originated from human cells (endometrium) or mouse cells (stroma). Four key pathways (ubiquitin/proteosome, inflammation, tissue remodelling/repair and ras-mediated oncogenesis) were revealed, that demonstrated communication between host stromal cells and ectopic endometrium. Morphometric analysis of nude mouse lesions confirmed that necrosis, inflammation, healing and repair and cell proliferation occurred during xenograft development. These processes were entirely consistent with the molecular networks revealed by the microarray data. The transcripts detected in the xenografts overlapped with transcripts differentially expressed in a comparison between paired eutopic and ectopic endometrium from human endometriotic patients. For the first time components of the interaction between ectopic endometrium and peritoneal stromal tissues have been revealed in ectopic endometrial lesions. Targeted disruption of this dialogue is likely to disrupt endometriotic tissue formation and may prove to be an effective therapeutic strategy for endometriosis. Experiment Overall Design: Xenografts of human endometrium in nude mice hybridised to both human and mouse specific genechips. 2 biological replicates, at 3 time points. Control human endometrium and mouse pertioneum were hybridised to both human and mouse genechips
2009-01-02 | E-GEOD-11768 | biostudies-arrayexpress
Project description:Eutopic endometrium (EuE) and endometriotic peritoneal lesions (ectopic endometrium, EcE) are heterogenous tissues according to the recent scRNA studies. We aimed to explore metabolic profile of cell populations in paired samples of EuE and EcE from four women with endometriosis. We found changes in the regulation of progesterone and estradiol signaling pathways in perivascular, stromal and endothelial cells of EcE compared to EuE, which might have a direct effect on cellular metabolism and contribute to cell proliferation and angiogenesis. The metabolic pathways were differentially regulated in perivascular, stromal and endothelial clusters, and metabolic pathway activity change between EcE and EuE was the highest for AMPK, HIF-1, glutathione metabolism, OXPHOS, and glycolysis/ gluconeogenesis. Remarkably, we identified co-activation of glycolysis and OXPHOS in perivascular and stromal cells of EcE compared to EuE. Previous studies reported a Warburg-like effect in endometriosis with a high use of glycolysis pathway over oxidative metabolism. Our observations might suggest the employment of both OXPHOS and glycolysis to meet the energy demands of proliferating cells in endometriotic lesions.
2024-07-21 | GSE247695 | GEO
Project description:Background: Newer 3D culturing approaches are a promising way to better mimic the in vivo tumor microenvironment and to study the interactions between the heterogeneous cell populations of glioblastoma multiforme. Like many other tumors, glioblastoma uses extracellular vesicles as an intercellular communication system to prepare surrounding tissue for invasive tumor growth. However, little is known about the effects of 3D culture on extracellular vesicles. The aim of this study was to comprehensively characterise extracellular vesicles in 3D organoid models and compare them to conventional 2D cell culture systems.Methods: Primary glioblastoma cells were cultured as 2D and 3D organoid models. Extracellular vesicles were obtained by precipitation and immunoaffinity, with the latter allowing targeted isolation of the CD9/CD63/CD81 vesicle subpopulation. Comprehensive vesicle characterisation was performed and miRNA expression profiles were generated by smallRNA-sequencing. In silico analysis of differentially regulated miRNAs was performed to identify mRNA targets and corresponding signaling pathways. The tumor cell media and extracellular vesicle proteome were analysed by high-resolution mass spectrometry.Results: We observed an increased concentration of extracellular vesicles in 3D organoid cultures. Differential gene expression analysis further revealed the regulation of twelve miRNAs in 3D tumor organoid cultures (with nine miRNAs down and three miRNAs upregulated). MiR-23a-3p, known to be involved in glioblastoma invasion, was significantly increased in 3D. MiR-7-5p, which counteracts glioblastoma malignancy, was significantly decreased. Moreover, we identified four miRNAs (miR- 323a-3p, miR-382-5p, miR-370-3p, miR-134-5p) located within the DLK1-DIO3 domain, a cancer associated genomic region, suggesting a possible importance of this region in glioblastoma progression. Overrepresentation analysis identified alterations of extracellular vesicle cargo in 3D organoids, including representation of several miRNA targets and proteins primarily implicated in the immune response.Conclusion: Our results show that 3D glioblastoma organoid models secrete extracellular vesicles with an altered cargo compared to corresponding conventional 2D cultures. Extracellular vesicles from 3D cultures were found to contain signaling molecules associated with the immune regulatory signaling pathways and as such could potentially change the surrounding microenvironment towards tumor progression and immunosuppressive conditions. These findings suggest the use of 3D glioblastoma models for further clinical biomarker studies as well as investigation of new therapeutic options.
2024-04-09 | PXD047328 | Pride