Gene expression profiling of C/EBPβ- and STAT3-deficient human endometrial stromal cells (HESC)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41473 | GEO | 2012/10/11
SECONDARY ACCESSION(S): PRJNA177117
REPOSITORIES: GEO
Similar Datasets
Project description:Our previous studies have shown that C/EBPM-NM-2 plays a critical role in human endometrial stromal decidualization. In order to identify the molecular pathways regulated by C/EBPM-NM-2 during decidualization, we performed gene expression profiling using RNA isolated from normal and C/EBPM-NM-2-deficient human endometrial stromal cells. The microarray results revealed that several key regulators of stromal differentiation, such as BMP2, Wnt4, IL-11RM-NM-1 and STAT3, operate downstream of C/EBPM-NM-2 during decidualization. Further studies revealed that STAT3 is a direct target of C/EBPM-NM-2 and plays an important role in cytokine signal during the decidualization process. Gene expression profiling, using STAT3-deficient HESCs, showed an extensive overlap of pathways downstream of STAT3 and C/EBPM-NM-2 during stromal cell differentiation. We employed a siRNA strategy to suppress C/EBPM-NM-2 or STAT3 mRNA expression in HESCs and then performed microarray analysis to identify its downstream target genes. Further, using a similar strategy, we focused on STAT3, a C/EBPM-NM-2 target gene, and identified the commone pathways downstream of both C/EBPM-NM-2 and STAT3.
2012-10-11 | E-GEOD-41473 | biostudies-arrayexpress
Project description:Our previous studies have shown that bone morphogenetic protein 2 (BMP2), a morphogen belonging to the TGFM-NM-2 superfamily, is markedly induced in human primary endometrial stromal cells (HESC) as they undergo differentiation in response to steroid hormones and cAMP. WNT4 is a downstream target of BMP2 regulation in these cells. To identify the common downstream targets of BMP2 and WNT4 in human endometrial stromal cells, we performed gene expression profling of human ensometrial stromal cell transduced with BMP2 or WNT4 adenovirus. Gene expression profiling revealed that FOXO1, a forkhead family transcription factor and a known regulator of HESC differentiation, is a common downstream mediator of both BMP2 and WNT4 signaling. These studies uncovered a linear pathway involving BMP2, WNT4, and FOXO1 that operates in human endometrium to critically control decidualization. Human endometrial stromal cells were transduced with recombinant adenovirus expressing BMP2, WNT4, or a negative control GFP at MOI 50:1 in 2 ml of culture medium. After transduction for 24 h, the viral particles were removed and the cells were treated with E+P for 3 days to induce decidualization (n=3 for each treatment), pooled total RNA from these cells was then hybridized to high density affymetrix microarrays according to the Affymetrix protocol (Human Genome HG-U133 A2.0 Array) .
2013-02-08 | E-GEOD-39949 | biostudies-arrayexpress
Project description:Our previous studies have shown that bone morphogenetic protein 2 (BMP2), a morphogen belonging to the TGFβ superfamily, is markedly induced in human primary endometrial stromal cells (HESC) as they undergo differentiation in response to steroid hormones and cAMP. WNT4 is a downstream target of BMP2 regulation in these cells. To identify the common downstream targets of BMP2 and WNT4 in human endometrial stromal cells, we performed gene expression profling of human ensometrial stromal cell transduced with BMP2 or WNT4 adenovirus. Gene expression profiling revealed that FOXO1, a forkhead family transcription factor and a known regulator of HESC differentiation, is a common downstream mediator of both BMP2 and WNT4 signaling. These studies uncovered a linear pathway involving BMP2, WNT4, and FOXO1 that operates in human endometrium to critically control decidualization.
2013-02-08 | GSE39949 | GEO
Project description:Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets.
2017-03-04 | GSE95666 | GEO
Project description:Proper decidualization is vital in preparation for a potential embryo receptivity, placentation, menstrual health and subsequent endometrial regeneration. Given the importance of extracellular vesicles (EVs) in intercellular communication, and recently in embryo implantation and indicators of menstrual cycle and fertility, we investigated their role during decidualization. Overall, this study provides an insight into distinct variation in sEV composition depending upon the level of decidualization of endometrial stromal cells, with the signaling potential to coordinate endometrial health ranging from embryo implantation, facilitating placentation and subsequent endometrial regeneration.
2021-11-17 | PXD026342 | Pride
Project description:To improve the understanding of PGRMC1 during decidualization, different in vitro decidualization protocols and global gene expression of endometrial stromal cells analysis were assessed.
2020-09-27 | GSE151650 | GEO
Project description:Ovarian estrogen (E2) and progesterone (P4) are indispensable for embryo-implantation and endometrial stromal decidualization; however, the molecular mechanisms that underpin these reproductive processes are unclear. Steroid receptor coregulator-2 (SRC-2) belongs to the multifunctional SRC/p160 family which also includes SRC-1 and SRC-3. Sharing strong sequence homology, all three SRCs exert diverse regulatory effects by modulating the transcriptional potency of nuclear receptor family members, including the estrogen and progesterone receptor (ER and PR respectively). Importantly, absence of SRC-2 in PR positive cells in the epithelial, stromal, and myometrial compartments of the murine uterus results in a striking infertility defect. This reproductive phenotype highlights a key role for SRC-2 in uterine function which is not shared with other coregulators. Intriguingly, abrogation of uterine SRC-2 does not block embryo apposition or attachment to the apical surface of luminal epithelial cells of the endometrium but rather prevents P4-dependent local decidualization of the sub-epithelial stroma. Remarkably, epithelial-specific ablation of SRC-2 in the murine uterus does not compromise endometrial functionality, again underscoring the unique importance of stromal derived SRC-2 in uterine function. The stromal decidualization defect resulting from SRC-2 ablation is reflected at the molecular level by a marked attenuation in P4 responsive target genes known to be critical for P4 dependent decidualization (i.e. ERBB receptor feedback inhibitor 1, Follistatin and Fkbp5). Conversely, the induction of E2 or P4 target genes involved in embryo implantation (i.e. leukemia inhibitory factor (LIF) and Indian hedgehog (Ihh) respectively) is not affected by SRC-2’s absence. As with mouse studies, decidualization of primary human stromal cells (HESCs) in culture is blocked by SRC-2 knockdown; however, HESC decidualization is unaffected by knockdown of SRC-1 or SRC-3. As a consequence of SRC-2 knockdown, molecular studies disclose a striking decrease in the induction of a subset of P4 target genes (i.e. WNT4 and FKBP5) which are essential for the stromal-epithelioid transformation step, the cellular hallmark of endometrial decidualization. Collectively, these studies not only showcase the evolutionary importance of SRC-2 in endometrial biology but also suggest that deregulation of this coregulator may underpin a spectrum of hormone-dependent uterine pathologies such as endometriosis and endometrial cancer. Microarray analysis was performed on mouse uteri using eighteen SRC-2flox/flox (SRC-2f/f) and eighteen PRCre/+ SRC-2flox/flox (SRC-2d/d) mice. Mice were ovariectomized at 6 weeks and after 2 weeks mice were either treated with sesame oil (vehicle) or 1 mg of P4. RNA from three mice per genotype per treatment were pooled and assigned as one sample (three samples per genotype per treatment). multiple group comparison
2014-04-01 | E-GEOD-31406 | biostudies-arrayexpress
Project description:To detect the direct target genes of SOX4 in differentiated human primary endometrial stromal cells, differentiated human primary endometrial stromal cells cells at the presence of MPA, E2 and cAMP are collected and subjected to ChIP-Seq. After aligned to human Hg38 by STAR, peaks are called by MACS2. Our results show that SOX4 is the key regulator for decidualization by regulating FOXO1, STAT3, PRL and FOSL2. This specific enrichment is confirmed by ChIP-qPCR. Additionally, there are also some other direct genes of SOX4, indicating the essential role of SOX4 in decidualization. This ChIP-Seq data provides fundamental information for our further physiological study of SOX4.
2022-01-28 | GSE195606 | GEO
Project description:Ovarian estrogen (E2) and progesterone (P4) are indispensable for embryo-implantation and endometrial stromal decidualization; however, the molecular mechanisms that underpin these reproductive processes are unclear. Steroid receptor coregulator-2 (SRC-2) belongs to the multifunctional SRC/p160 family which also includes SRC-1 and SRC-3. Sharing strong sequence homology, all three SRCs exert diverse regulatory effects by modulating the transcriptional potency of nuclear receptor family members, including the estrogen and progesterone receptor (ER and PR respectively). Importantly, absence of SRC-2 in PR positive cells in the epithelial, stromal, and myometrial compartments of the murine uterus results in a striking infertility defect. This reproductive phenotype highlights a key role for SRC-2 in uterine function which is not shared with other coregulators. Intriguingly, abrogation of uterine SRC-2 does not block embryo apposition or attachment to the apical surface of luminal epithelial cells of the endometrium but rather prevents P4-dependent local decidualization of the sub-epithelial stroma. Remarkably, epithelial-specific ablation of SRC-2 in the murine uterus does not compromise endometrial functionality, again underscoring the unique importance of stromal derived SRC-2 in uterine function. The stromal decidualization defect resulting from SRC-2 ablation is reflected at the molecular level by a marked attenuation in P4 responsive target genes known to be critical for P4 dependent decidualization (i.e. ERBB receptor feedback inhibitor 1, Follistatin and Fkbp5). Conversely, the induction of E2 or P4 target genes involved in embryo implantation (i.e. leukemia inhibitory factor (LIF) and Indian hedgehog (Ihh) respectively) is not affected by SRC-2’s absence. As with mouse studies, decidualization of primary human stromal cells (HESCs) in culture is blocked by SRC-2 knockdown; however, HESC decidualization is unaffected by knockdown of SRC-1 or SRC-3. As a consequence of SRC-2 knockdown, molecular studies disclose a striking decrease in the induction of a subset of P4 target genes (i.e. WNT4 and FKBP5) which are essential for the stromal-epithelioid transformation step, the cellular hallmark of endometrial decidualization. Collectively, these studies not only showcase the evolutionary importance of SRC-2 in endometrial biology but also suggest that deregulation of this coregulator may underpin a spectrum of hormone-dependent uterine pathologies such as endometriosis and endometrial cancer.
2014-04-01 | GSE31406 | GEO
Project description:Dramatic changes of gene expressions are known to occur in human endometrial stromal cells (ESC) during decidualization. The changes in gene expression are associated with changes of chromatin structure, which are regulated by epigenetic mechanisms such as histone modifications. Here, we investigated genome-wide changes in histone modifications and mRNA expressions associated with decidualization in human ESC using chromatin immunoprecipitation (ChIP) combined with next-generation sequencing. ESC were incubated with estradiol and medroxyprogesterone acetate for 14 days to induce decidualization. The ChIP-sequence data showed that induction of decidualization increased H3K27ac and H3K4me3 signals in many genomic regions but decreased in only a few regions. Most (80%) of the H3K27ac-increased regions and half of the H3K4me3-increased regions were located in the distal promoter regions (more than 3 kb upstream or downstream of the transcription start site). RNA-sequence showed that induction of decidualization up-regulated 881 genes, 223 of which had H3K27ac- or H3K4me3-increased regions in the proximal and distal promoter regions. Induction of decidualization increased the mRNA levels of these genes more than it increased the mRNA levels of genes without H3K27ac- or H3K4me3-increased regions. Pathway analysis revealed that up-regulated genes with the H3K27ac- or H3K4me3-increased regions were associated with insulin signaling. These results show that histone modification statuses genome-widely change in human ESC by induction of decidualization. The main changes of histone modifications are increases of H3K27ac and H3K4me3 in both the proximal and distal promoter regions, which are involved in the up-regulation of gene expression that occurs during decidualization. mRNA profiles of human endometrial stromal cells with and without EP inductions for 2 individuals. (EP induction: induction with estradiol (10-8 M) and medroxyprogesterone acetate (10-6 M))
2015-03-03 | E-GEOD-57009 | biostudies-arrayexpress