TCF21 orchestrates epithelial-to-mesenchymal transition and cytoskeleton reorganization in uterine development and endometriosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE282592 | GEO | 2025/11/20
REPOSITORIES: GEO
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Project description:TCF21 orchestrates epithelial-to-mesenchymal transition and cytoskeleton reorganization in uterine development and endometriosis
| PRJNA1189432 | ENA
Project description:Endometriosis is an estrogen-dependent inflammatory disease. A pivotal contributor to endometriosis is the estrogen receptor beta (ERβ), which drives the condition by impeding cell death through interferon (IFN) signaling. One noteworthy component of this cascade is the N-myc and STAT Interactor (NMI), an interferon alpha (IFNα) target gene whose expression is repressed in endometriotic lesions compared to normal endometrium. This repression is particularly pronounced in stromal cells, mediated by ERβ. The results of Western blot analyses, comparing IFNα-treated and untreated cells, demonstrate that IFNα treatment triggers cell death signaling, including apoptosis and necroptosis, in endometrial stromal cells. Intriguingly, NMI knockdown (KD) obstructed IFNα-induced cell death signaling in human endometrial stromal cells. Moreover, NMI KD amplified non-canonical IFNα pathways, such as β-Catenin/GSK3β and PI3K/AKT signaling, in endometrial stromal cells following IFNα treatment. RNA sequencing analyses unveiled that NMI KD augmented the expression of genes responsible for cell-cell adhesion and extracellular structural organization in IFNα-independent manners. These findings suggest that NMI KD plays an indispensable role in enhancing the adhesion and invasion of endometriotic cells during endometriosis progression. In summary, NMI functions as an endometriosis suppressor gene in endometriotic stromal cells, curbing the advancement of endometriosis. This intricate interplay of ERβ, IFNα signaling, and NMI offers novel insights into the mechanisms governing endometriosis development.
2025-08-31 | GSE241751 | GEO
Project description:Endometriosis shows significant lesion heterogeneity, but pathophysiological mechanisms leading to differences in clinical presentation are poorly understood. Here we utilized primary stromal cells from different types of endometriotic lesions to better understand the molecular mechanisms that lead to endometriosis heterogeneity. For this project, endometrial stromal cells (ESCs) were obtained from eutopic endometrium (EU), endometrioma (OMA), superficial (SF) and deep (DE) endometriosis lesions and analyzed in vitro for their behavior regarding proliferation, migration, and contractility. RNA sequencing was performed to explore the molecular mechanism underlying the observed changes.
2025-12-17 | GSE303635 | GEO
Project description:Accumulating evidences suggest that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis. The aim of this study is to identify 1) the panel of aberrantly expressed genes that are epigenetically suppressed by histone acetylation in endometriosis; 2) the roles of CCAAT/enhancer-binding protein (C/EBP) alpha, one of the candidate molecules whose expression was epigenetically repressed in endometriotic cyst stromal cells (ECSCs), in the pathogenesis of endometriosis; and 3) the efficacy of the histone deacetylase inhibitors for the treatment of endometriosis. Subconfluent ECSCs cultured in 10-cm dish were further incubated for 72 h with or without VPA (8 mM) and/or 5aza. Total RNA from untreated ECSCs (n=4), VPA-treated ECSCs (n=4), 5aza-treated ECSCs (n=4), and VPA- and 5aza-treated ECSCs (n=4) was extracted and subjected to gene expression microarray analysis.
2013-10-21 | E-GEOD-44207 | biostudies-arrayexpress
Project description:Accumulating evidences suggest that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis. The aim of this study is to identify 1) the panel of aberrantly expressed genes that are epigenetically suppressed by histone acetylation in endometriosis; 2) the roles of CCAAT/enhancer-binding protein (C/EBP) alpha, one of the candidate molecules whose expression was epigenetically repressed in endometriotic cyst stromal cells (ECSCs), in the pathogenesis of endometriosis; and 3) the efficacy of the histone deacetylase inhibitors for the treatment of endometriosis.
2013-10-21 | GSE44207 | GEO
Project description:Background Reduced endometrial receptivity is a major factor for impaired fertility in endometriosis (EMS). Endometrial deposition of collagen I proteins may account for poor endometrial receptivity in endometriosis. Methods We investigated the expression of collagen I expression in endometrium of endometriosis patients and in constructed EMS mice model. Effect of collagen I on ESCs was evaluated. Co-culture of exosomes with ESCs was conducted to evaluate the uptake of exosomes by different endometrial cell lines and the effect on decidualization of eutopic ESCs and embryo implantation. MiRNA expression profiles were compared between ectopic ESC derived exosomes and eutopic ESC derived exosomes. Luciferase reporter and its mutant plasmids were applied to confirm the direct target of miR-25-3p. Findings Here we found endometrial collagen I deposition with impaired decidualization in endometriosis patients and EMS mice model. Treatment of collagen I with ESCs contributed to impaired decidualization and inhibited BLS expansion in vitro. Endometriotic stromal cell-derived exosomes were detected in eutopic endometrium and the ectopic endometrial stromal cell derived exosomes were more taken-up by the same cell line in eutopic endometrium. Treatment of endometriotic stromal cell-derived exosomes increased the expression of endometrial collagen I in vitro and in vivo, while inhibited BLS expansion. Exosomal miR-25-3p was significantly increased in endometriotic stromal cell-derived exosomes compared with control group, and PTEN is a certain target of miR-25-3p. The promotion of endometrial miR-25-3p significantly increased collagen I expression in vitro through the PTEN/Akt pathway. Interpretation These results suggested that endometriotic stromal cell-derived exosomal miR-25-3p played key role in inducing endometrial collagen I deposition to impair embryo expansion in endometriosis via PTEN/Akt pathway. Funding National Nature Science Foundation of China (82271702), National Natural Science Foundation of China (81771537). Keywords: endometriosis; exosome; collagen I; miRNA; collagen deposition
2025-01-28 | GSE222432 | 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:Uterine Atlas Endometriosis
Endometriosis is a chronic inflammatory disease driven by oestrogen, affecting around 10% of women of child-bearing again world-wide. It is described by the presence of endometrium-like tissue outside of the uterus (ectopic endometriosis tissue) and debilitating chronic pain. There is a lack of understanding of endometriosis pathogenesis, as well as cellular composition of both the eutopic endometrium and ectopic endometriosis tissue of endometriosis patients.There are therefore two main aims for this study. Using single cell genomics and spatial methods we aim to:
I) characterise endometrial cellular census in women with and without endometriosis
II) characterise cellular census of ectopic endometriosis tissue
Furthermore, we aim to establish endometrial organoids and endometriosis organoids from the samples collected and characterise these using single cell genomics and spatial methods.
This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
| EGAS00001004725 | EGA
Project description:Pyruvate carboxylase (PC) is a key metabolic enzyme, and its role in endometriosis progression remains unclear. This study aimed to investigate whether PC promotes endometriosis progression and explore its underlying mechanisms. Immunohistochemical analysis was used to detect PC expression in patient tissues; PC was knocked down or overexpressed in immortalized human endometriotic stromal cells (ihESCs) to assess proliferation (colony formation, EdU assay) and migration (Transwell assay) changes. Quasi-targeted metabolomics and RNA sequencing were applied to explore the effects of PC knockdown on downstream metabolism and pathways, and Western blotting was used to detect related protein changes. Additionally, an allogeneic endometriosis model in C57BL/6J female mice with AAV9-mediated PC overexpression was established to verify PC's in vivo effect. Results showed that PC expression was significantly upregulated in endometriosis patients; in vitro and in vivo experiments confirmed PC promotes endometriosis progression. Quasi-targeted metabolomics revealed PC enhances ihESCs glycolysis, while RNA sequencing and western blotting identified PC activates the PI3K-AKT pathway. Further studies with AKT agonist (SC79) and inhibitor (AZD5363) demonstrated PC promotes endometriosis glycolysis and progression via the AKT pathway. Moreover, PC inhibitors ZY-444 and octyl gallate inhibited ihESCs proliferation and migration, and ZY-444 suppressed endometriotic lesion growth in mice.
2026-01-11 | GSE316028 | GEO
Project description:Endometriosis shows significant lesion heterogeneity, but pathophysiological mechanisms leading to differences in clinical presentation are poorly understood. Here we utilized primary stromal cells from different types of endometriotic lesions to better understand the molecular mechanisms that lead to endometriosis heterogeneity. For this aim, endometrial stromal cells (ESCs) were obtained from eutopic endometrium (EU), endometrioma (OMA), superficial (SF) and deep (DE) endometriosis lesions and analyzed in vitro for their behavior regarding proliferation, migration, and contractility. Proteomics was used to explore the molecular mechanism underlying the observed changes.
2025-12-15 | PXD066685 | Pride