Endometrial epithelial Arid1a is essential in early pregnancy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA805186 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Endometrial epithelial Arid1a is necessary for normal gene expression and maintenance of a receptive endometrium at pre-implantation stage in mice. We used RNA-sequencing to determine the differences in uterine gene expression resulting from deletion of endometrial epithelial Arid1a.
2022-03-01 | GSE196489 | GEO
Project description:Arid1a has a critical role for modulating epithelial proliferation which is a critical requisite for fertility We used microarrays for detail the mechanism underlying Arid1a loss during early pregnancy.
2015-08-20 | GSE72200 | GEO
Project description:Arid1a is essential for endometrial gland development
| PRJNA564689 | ENA
Project description:Arid1a has a critical role for modulating endometrial gland develop that is required for normal uterine function and fertility after maturity. We used microarrays to detail the mechanism underlying Arid1a loss during postnatal development.
2019-11-06 | GSE137166 | GEO
Project description:Pregnancy loss is the most common complication of human pregnancy. Recurrent early pregnancy loss (REPL) has multiple etiologies, including endometrial dysregulation leading to “suboptimal” implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown. We hypothesized that genes that gained novel expression in the endometria of mammals that evolved in the Eutherian stemlineage, coincident with the evolution of pregnancy, are likely essential for establishment and maintenance of normal pregnancy and are, therefore, good candidates for genes whose expression may be dysregulated in disorders such as REPL. To test this hypothesis, we took an evolutionary forward genomics approach to characterize gene expression profiles of midsecretory endometria from women with REPL associated with abnormal endometria based either on histology or molecular expression of cyclin E. We identified 58 genes that were differentially expressed (P<0.001) between women with out-of-phase histological dating vs normal histology, and 81 genes that were differentially expressed (P<0.001) between women with abnormally elevated cyclin E levels vs normal cyclin E. Remarkably, genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P=0.002 for histology, P=0.021 for cyclin E), as well as for immune and signaling pathways with essential roles in endometrial biology. Thus, our novel evolutionary-based forward genomics approach identified genes whose dysregulation during the mid-secretory phase likely contributes to the molecular etiologies of recurrent early pregnancy loss. Total RNA obtained from mid luteal phase endometrium (two replicates per biopsy) from women with recurrent early pregnancy loss (REPL). Endometrial gene expression levels were compared 1) between women with out-of-phase (n=10) and normal histological dating (n=22), 2) between women with abnormally elevated (n=9) and normal (n=23) cyclin E levels. For 5 additional women with abnormally high cyclin E levels, biopsy samples were collected before and after progesterone treatment to investigate the gene expression profiles in response to progesterone.
2014-12-06 | E-GEOD-63901 | biostudies-arrayexpress
Project description:Pregnancy loss is the most common complication of human pregnancy. Recurrent early pregnancy loss (REPL) has multiple etiologies, including endometrial dysregulation leading to “suboptimal” implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown. We hypothesized that genes that gained novel expression in the endometria of mammals that evolved in the Eutherian stemlineage, coincident with the evolution of pregnancy, are likely essential for establishment and maintenance of normal pregnancy and are, therefore, good candidates for genes whose expression may be dysregulated in disorders such as REPL. To test this hypothesis, we took an evolutionary forward genomics approach to characterize gene expression profiles of midsecretory endometria from women with REPL associated with abnormal endometria based either on histology or molecular expression of cyclin E. We identified 58 genes that were differentially expressed (P<0.001) between women with out-of-phase histological dating vs normal histology, and 81 genes that were differentially expressed (P<0.001) between women with abnormally elevated cyclin E levels vs normal cyclin E. Remarkably, genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P=0.002 for histology, P=0.021 for cyclin E), as well as for immune and signaling pathways with essential roles in endometrial biology. Thus, our novel evolutionary-based forward genomics approach identified genes whose dysregulation during the mid-secretory phase likely contributes to the molecular etiologies of recurrent early pregnancy loss.
2014-12-06 | GSE63901 | GEO
Project description: Not available
| S-EPMC4574948 | biostudies-literature
Project description:Endometriosis affects 1-in-10 women and is characterized by the presence of abnormal endometrium at ectopic sites. ARID1A mutations are observed in deeply invasive forms of the disease, often correlating with malignancy. To identify epigenetic dependencies driving invasion, we utilized an unbiased approach to map chromatin state transitions accompanying ARID1A loss in the endometrium. We show that super-enhancers marked by high H3K27-acetylation are strongly associated with ARID1A binding. ARID1A loss leads to H3K27-hyperacetylation and increased chromatin accessibility and enhancer RNA transcription at super-enhancers, but not typical enhancers, indicating that ARID1A normally prevents super-enhancer hyperactivation. ARID1A co-localizes with P300 at super-enhancers, and genetic or pharmacological inhibition of P300 in ARID1A-mutant endometrial epithelia suppresses invasion and induces anoikis through rescue of super-enhancer hyperacetylation. Among hyperactivated super-enhancers, SERPINE1 (PAI-1) was identified as an essential target gene driving ARID1A-mutant endometrial invasion. Broadly, our findings provide rationale for therapeutic strategies targeting super-enhancers in ARID1A-mutant endometrium.
2020-11-10 | GSE157731 | GEO
Project description:Endometriosis affects 1-in-10 women and is characterized by the presence of abnormal endometrium at ectopic sites. ARID1A mutations are observed in deeply invasive forms of the disease, often correlating with malignancy. To identify epigenetic dependencies driving invasion, we utilized an unbiased approach to map chromatin state transitions accompanying ARID1A loss in the endometrium. We show that super-enhancers marked by high H3K27-acetylation are strongly associated with ARID1A binding. ARID1A loss leads to H3K27-hyperacetylation and increased chromatin accessibility and enhancer RNA transcription at super-enhancers, but not typical enhancers, indicating that ARID1A normally prevents super-enhancer hyperactivation. ARID1A co-localizes with P300 at super-enhancers, and genetic or pharmacological inhibition of P300 in ARID1A-mutant endometrial epithelia suppresses invasion and induces anoikis through rescue of super-enhancer hyperacetylation. Among hyperactivated super-enhancers, SERPINE1 (PAI-1) was identified as an essential target gene driving ARID1A-mutant endometrial invasion. Broadly, our findings provide rationale for therapeutic strategies targeting super-enhancers in ARID1A-mutant endometrium.
2020-11-10 | GSE157735 | GEO
Project description:Endometriosis affects 1-in-10 women and is characterized by the presence of abnormal endometrium at ectopic sites. ARID1A mutations are observed in deeply invasive forms of the disease, often correlating with malignancy. To identify epigenetic dependencies driving invasion, we utilized an unbiased approach to map chromatin state transitions accompanying ARID1A loss in the endometrium. We show that super-enhancers marked by high H3K27-acetylation are strongly associated with ARID1A binding. ARID1A loss leads to H3K27-hyperacetylation and increased chromatin accessibility and enhancer RNA transcription at super-enhancers, but not typical enhancers, indicating that ARID1A normally prevents super-enhancer hyperactivation. ARID1A co-localizes with P300 at super-enhancers, and genetic or pharmacological inhibition of P300 in ARID1A-mutant endometrial epithelia suppresses invasion and induces anoikis through rescue of super-enhancer hyperacetylation. Among hyperactivated super-enhancers, SERPINE1 (PAI-1) was identified as an essential target gene driving ARID1A-mutant endometrial invasion. Broadly, our findings provide rationale for therapeutic strategies targeting super-enhancers in ARID1A-mutant endometrium.
2020-11-10 | GSE157732 | GEO