Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA297282 | ENA |
REPOSITORIES: ENA
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Project description:Estrogen and progesterone are important regulators of human endometrial differentiation. These steroid hormones act, at least in part, through their nucelar receptors. Role of estrogen receptor alpha (ESR1) during human endometrial differentiation is still unclear. We used microarray analysis to detail the gene expression regulated by ESR1 during differentiation of human endometrial stromal cells.
2016-12-22 | GSE73550 | GEO
Project description:Estrogen (E2) acting through the estrogen receptor alpha (ESR1) is a critical regulator of endometrial growth, differentiation and disease. The endometrial stromal cell (ESC) is a key target of ESR1 action and plays a crucial role in regulating paracrine communication to control uterine function. A mechanistic understanding of the role of ESR1 in ESCs is limited by low levels of expression of ESC lines. Here we engineered telomerase-immortalized hESC (THESC) to express the CRISPR activation system to activate ESR1. Among six tested guide RNAs, the ESR1-3 gRNA induced robust ESR1 activation, restoring E2 responsiveness in THESC. Bulk RNA-seq revealed ESR1-mediated E2-dependent and E2-independent transcriptional programs, regulating pathways involved in inflammation, proliferation, extracellular matrix organization, and cancer. Notably, 72% of differentially expressed genes (DEGs) overlapped with genes active in human endometrial tissue during the proliferative E2 dominant phase, supporting their physiological relevance. Cut&Run-seq identified genome-wide ESR1 binding sites, with most located at distal regulatory elements. To associate distal ESR1 binding sites with genes, we integrated H3K27ac HiChIP chromatin loops in hESC to identify distal ESR1 binding sites that loop to gene promoters. We identified genes regulated by ESR1/E2 through long-range chromatin looping that are involved in stromal cell decidualization, including FOXO1 and IL6R. Additionally, we identified genes implicated in endometrial cancer, including ERRFI1, NRIP1, and EPAS1, suggesting a role for stromal ESR1 driven endometrial pathologies. Functional assays confirmed that ESR1 promotes cell viability and, in the presence of E2, enhances migration. In this study, we reveal novel insights into ESR1-dependent transcriptional regulation using a newly developed cell culture model that restores ESR1 expression in hESCs to overcome their limited E2 responsiveness. Additionally, we demonstrate the utility of integrating HiChIP chromatin looping data with cistromic data to associate distal ESR1 binding sites to gene promoters.
2025-05-12 | GSE295511 | GEO
Project description:Estrogen (E2) acting through the estrogen receptor alpha (ESR1) is a critical regulator of endometrial growth, differentiation and disease. The endometrial stromal cell (ESC) is a key target of ESR1 action and plays a crucial role in regulating paracrine communication to control uterine function. A mechanistic understanding of the role of ESR1 in ESCs is limited by low levels of expression of ESC lines. Here we engineered telomerase-immortalized hESC (THESC) to express the CRISPR activation system to activate ESR1. Among six tested guide RNAs, the ESR1-3 gRNA induced robust ESR1 activation, restoring E2 responsiveness in THESC. Bulk RNA-seq revealed ESR1-mediated E2-dependent and E2-independent transcriptional programs, regulating pathways involved in inflammation, proliferation, extracellular matrix organization, and cancer. Notably, 72% of differentially expressed genes (DEGs) overlapped with genes active in human endometrial tissue during the proliferative E2 dominant phase, supporting their physiological relevance. Cut&Run-seq identified genome-wide ESR1 binding sites, with most located at distal regulatory elements. To associate distal ESR1 binding sites with genes, we integrated H3K27ac HiChIP chromatin loops in hESC to identify distal ESR1 binding sites that loop to gene promoters. We identified genes regulated by ESR1/E2 through long-range chromatin looping that are involved in stromal cell decidualization, including FOXO1 and IL6R. Additionally, we identified genes implicated in endometrial cancer, including ERRFI1, NRIP1, and EPAS1, suggesting a role for stromal ESR1 driven endometrial pathologies. Functional assays confirmed that ESR1 promotes cell viability and, in the presence of E2, enhances migration. In this study, we reveal novel insights into ESR1-dependent transcriptional regulation using a newly developed cell culture model that restores ESR1 expression in hESCs to overcome their limited E2 responsiveness. Additionally, we demonstrate the utility of integrating HiChIP chromatin looping data with cistromic data to associate distal ESR1 binding sites to gene promoters.
2025-05-12 | GSE295510 | GEO
Project description:Estrogen (E2) acting through the estrogen receptor alpha (ESR1) is a critical regulator of endometrial growth, differentiation and disease. The endometrial stromal cell (ESC) is a key target of ESR1 action and plays a crucial role in regulating paracrine communication to control uterine function. A mechanistic understanding of the role of ESR1 in ESCs is limited by low levels of expression of ESC lines. Here we engineered telomerase-immortalized hESC (THESC) to express the CRISPR activation system to activate ESR1. Among six tested guide RNAs, the ESR1-3 gRNA induced robust ESR1 activation, restoring E2 responsiveness in THESC. Bulk RNA-seq revealed ESR1-mediated E2-dependent and E2-independent transcriptional programs, regulating pathways involved in inflammation, proliferation, extracellular matrix organization, and cancer. Notably, 72% of differentially expressed genes (DEGs) overlapped with genes active in human endometrial tissue during the proliferative E2 dominant phase, supporting their physiological relevance. Cut&Run-seq identified genome-wide ESR1 binding sites, with most located at distal regulatory elements. To associate distal ESR1 binding sites with genes, we integrated H3K27ac HiChIP chromatin loops in hESC to identify distal ESR1 binding sites that loop to gene promoters. We identified genes regulated by ESR1/E2 through long-range chromatin looping that are involved in stromal cell decidualization, including FOXO1 and IL6R. Additionally, we identified genes implicated in endometrial cancer, including ERRFI1, NRIP1, and EPAS1, suggesting a role for stromal ESR1 driven endometrial pathologies. Functional assays confirmed that ESR1 promotes cell viability and, in the presence of E2, enhances migration. In this study, we reveal novel insights into ESR1-dependent transcriptional regulation using a newly developed cell culture model that restores ESR1 expression in hESCs to overcome their limited E2 responsiveness. Additionally, we demonstrate the utility of integrating HiChIP chromatin looping data with cistromic data to associate distal ESR1 binding sites to gene promoters.
2025-05-12 | GSE295509 | GEO
Project description:Endometrial estrogen receptor-α (ESR1) is indispensable for epithelial and stromal proliferation and differentiation during decidualization, yet the gene targets of estradiol (E2) / ESR1 in human stromal cells and associated mechanisms remain unknown. In this study, we characterized global E2-ESR1‒dependent transcriptomic changes and ESR1 recruitment to chromatin. Human endometrial stromal cells were isolated from 4 premenopausal women for primary cell culture. Genome-wide RNA expression by RNA-sequencing was compared in endometrial stromal cells with or without siRNA knockdown of ESR1 in the presence or absence of E2 (n=2). Genome-wide recruitment of ESR1 to chromatin was assessed by chromatin immunoprecipitation sequencing using an antibody against ESR1 was performed to examine binding to target genes (n=1).
2020-07-06 | GSE151392 | GEO
Project description:Endometrial estrogen receptor-α (ESR1) is indispensable for epithelial and stromal proliferation and differentiation during decidualization, yet the gene targets of estradiol (E2) / ESR1 in human stromal cells and associated mechanisms remain unknown. In this study, we characterized global E2-ESR1‒dependent transcriptomic changes and ESR1 recruitment to chromatin. Human endometrial stromal cells were isolated from 4 premenopausal women for primary cell culture. Genome-wide RNA expression by RNA-sequencing was compared in endometrial stromal cells with or without siRNA knockdown of ESR1 in the presence or absence of E2 (n=2). Genome-wide recruitment of ESR1 to chromatin was assessed by chromatin immunoprecipitation sequencing using an antibody against ESR1 was performed to examine binding to target genes (n=1).
2020-07-06 | GSE151393 | GEO
Project description:Postnatal development of the uterus involves specification of undifferentiated epithelium into uterine-type epithelium. That specification is regulated by stromal-epithelial interactions as well as intrinsic cell-specific transcription factors and gene regulatory networks. This study utilized mouse genetic models of Esr1 deletion, endometrial epithelial organoids (EEO), and organoid-stromal co-cultures to decipher the role of Esr1 in uterine epithelial development. Organoids derived from wild-type (WT) mice developed a normal single layer of columnar epithelium. In contrast, EEO from Esr1 null mice developed a multilayered stratified squamous type of epithelium with basal cells. Co-culturing Esr1 null epithelium with WT uterine stromal fibroblasts inhibited basal cell development. Of note, estrogen treatment of EEO-stromal co-cultures and Esr1 conditional knockout mice increased basal epithelial cell markers. Collectively, these findings suggest that Esr1 regulates uterine epithelium lineage plasticity and homeostasis and loss of ESR1 promotes altered luminal-to-basal differentiation driven by ESR1-mediated paracrine factors from the stroma.
2023-08-02 | GSE232655 | GEO
Project description:Endometriosis is an inflammatory disease and bone marrow-derived cells are abundant in endometriotic lesions and in the peritoneal fluid of women with the disease. This study tested the hypothesis that reciprocal communication occurs between macrophages and cultured human endometrial stromal cells and that this communication contributes to the pathology of endometriosis. Changes in gene expression elicited by exposure to factors secreted by the opposing cell type were measured by DNA microarray to test this hypothesis. 716 named genes were differentially expressed in cultured endometrial stromal cells in response to factors secreted by macrophages. Genes that were up-regulated included IL8/CXCL8, MMP3, phospholamban, CYR61/CCN1, CTGF/CCN2, tenascin C, and NNMT, whereas integrin alpha 6 was down-regulated. In contrast, 15 named genes were differentially expressed in macrophages in response to factors secreted by cultured endometrial stromal cells. The data document reciprocal communication between macrophages and endometrial stromal cells and suggest that interaction with macrophages stimulates the expression of genes in endometrial stromal cells that contribute to migration, adhesion, invasion, neovascularization and mitosis of endometrial cells that may support the establishment of endometriosis.
2010-07-21 | GSE19834 | GEO
Project description:Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells.
2019-06-11 | GSE132428 | GEO
Project description:Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells.
2019-06-11 | GSE132426 | GEO