Expression data from in vitro decidualized human uterine fibroblast cells (HuF cells) with or without NOTCH1 silencing
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE61827 | GEO | 2014/09/30
SECONDARY ACCESSION(S): PRJNA262499
REPOSITORIES: GEO
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Project description:Decidualization is a critical process for embryo implatation during which uterine stromal fibroblasts are transformed into large, epithelioid-like decidual cell. NOTCH1 is recepotor of Notch signaling that plays important roles for cell-cell communication, which involves gene regulatory mechanisms that control multiple cellular differentiation processes during embryonic and adult life. Here we silenced NOTCH1 by shRNA in HuF cells and studied how it affects decidualization HuF cells were cultured, transfected with NOTCH1 shRNA via a lentivirus system, following by a in vitro induced decidualization by EPC cocktail (36 nM estradiol-17β and 1 μM medroxyprogesterone acetate, and 0.1 mM dbcAMP) for 6 days. RNAs were extracted then hybridized on Affymetrix microarrays. There are four experimental conditions: 1) transfected with empty plasmid; 2) transfected with hNOTCH1 lentiviral-shRNA plasmid; 3) transfected with empty plasmid and treated with EPC cocktail; and 4) hNOTCH1 lentiviral-shRNA plasmid with subsequent treatment of EPC cocktail. HuF cells from two different patients were used in each group (HuF86P4 & HuF88P4).
2014-09-30 | E-GEOD-61827 | biostudies-arrayexpress
Project description:Pausing of RNA polymerase II (Pol II) during early transcription, mediated by the negative elongation factor (NELF) complex, allows cells to coordinate and appropriately respond to signals by modulating the rate of transcriptional pause release. Promoter proximal enrichment of Pol II occurs at uterine genes relevant to reproductive biology; thus, we hypothesized that pausing might impact endometrial response by coordinating hormonal signals involved in establishing and maintaining pregnancy.We deleted the NELF-B subunit in themouse uterus using PgrCre (NELF-B UtcKO).Resulting females were infertile.Uterine response to the initial decidual stimulus of NELF-B UtcKOwas similar to that of control mice; however, subsequent full decidual response was not observed. Cultured NELF-B UtcKO stromal cells exhibited perturbances in extracellular matrix components and also expressed elevated levels of the decidual prolactin Prl8a2, as well as altered levels of transcripts encoding enzymes involved in prostaglandin synthesis and metabolism. Because endometrial stromal cell decidualization is also critical to human reproductive health and fertility, we used small interfering to suppressNELF-B or NELF-E subunits in cultured human endometrial stromal cells, which inhibited decidualization, as reflected by the impaired induction of decidual markers PRL and IGFBP1. Overall, our study indicatesNELF-mediated pausing is essential to coordinate endometrial responses and that disruption impairs uterine decidual development during pregnancy.
2018-11-07 | GSE122262 | GEO
Project description:Uterine receptivity implies a dialogue between the hormonally primed maternal endometrium and the free-floating blastocyst. Endometrial stromal cells proliferate, avert apoptosis, and undergo decidualization in preparation for implantation; however, the molecular mechanisms that underlie differentiation into the decidual phenotype remain largely undefined. The Notch family of transmembrane receptors transduce extracellular signals responsible for cell survival, cell-to-cell communication, and trans-differentiation, all fundamental processes for decidualization and pregnancy. Using a murine artificial decidualization model, pharmacological inhibition of Notch signaling by gamma-secretase inhibition resulted in significantly decreased deciduoma. Furthermore, a progesterone receptor (PR)-Cre Notch1 bigenic (Notch1d/d) confirmed a Notch1-dependant hypomorphic decidual phenotype. Microarray and pathway analysis, following Notch1 ablation, demonstrated significantly altered signaling repertoire. Concomitantly, hierarchical clustering demonstrated Notch1-dependent differences in gene expression. Uteri deprived of Notch1 signaling demonstrated decreased cellular proliferation; namely, reduced proliferation-specific antigen, Ki67, altered p21, cdk6, and cyclinD activity, and increased apoptotic-profile, augmented cleaved caspase-3, Bad, and attenuated Bcl2. Demonstrated here, the pre-implantation uterus relies on Notch signaling to inhibit apoptosis of stromal fibroblasts and regulate cell cycle progression, which together promotes successful decidualization. In summary, Notch1 signaling modulates multiple signaling mechanisms crucial for decidualization and we provide greater perspective to the coordination of multiple signaling modalities required during decidualization RNA samples from 3-5 separate mice were extracted. All mRNA quantities were normalized against 18S gene expression. Gene expression levels were measured by real-time RT-PCR SYBR Green analysis using the ABI Prism 7700 Sequence Detector System according to manufacturer’s instructions (Applied Biosystems).
2011-08-08 | E-GEOD-31244 | biostudies-arrayexpress
Project description:Uterine receptivity implies a dialogue between the hormonally primed maternal endometrium and the free-floating blastocyst. Endometrial stromal cells proliferate, avert apoptosis, and undergo decidualization in preparation for implantation; however, the molecular mechanisms that underlie differentiation into the decidual phenotype remain largely undefined. The Notch family of transmembrane receptors transduce extracellular signals responsible for cell survival, cell-to-cell communication, and trans-differentiation, all fundamental processes for decidualization and pregnancy. Using a murine artificial decidualization model, pharmacological inhibition of Notch signaling by gamma-secretase inhibition resulted in significantly decreased deciduoma. Furthermore, a progesterone receptor (PR)-Cre Notch1 bigenic (Notch1d/d) confirmed a Notch1-dependant hypomorphic decidual phenotype. Microarray and pathway analysis, following Notch1 ablation, demonstrated significantly altered signaling repertoire. Concomitantly, hierarchical clustering demonstrated Notch1-dependent differences in gene expression. Uteri deprived of Notch1 signaling demonstrated decreased cellular proliferation; namely, reduced proliferation-specific antigen, Ki67, altered p21, cdk6, and cyclinD activity, and increased apoptotic-profile, augmented cleaved caspase-3, Bad, and attenuated Bcl2. Demonstrated here, the pre-implantation uterus relies on Notch signaling to inhibit apoptosis of stromal fibroblasts and regulate cell cycle progression, which together promotes successful decidualization. In summary, Notch1 signaling modulates multiple signaling mechanisms crucial for decidualization and we provide greater perspective to the coordination of multiple signaling modalities required during decidualization
2011-08-09 | GSE31244 | GEO
Project description:Maternal-stroma derived decidual cells are the single population in the canine placenta expressing the nuclear progesterone (P4) receptor (PGR), rendering them crucial for the maintenance of canine pregnancy. Indeed, decreased circulating P4 levels or blockage of PGR function with antigestagens (e.g., aglepristone), culminates in the termination of canine pregnancy. As an in vitro model for canine decidualization, dog uterine stromal (DUS; Graubner et al., 2017) cells can be decidualized in vitro with cAMP. The antigestagens aglepristone and mifepristone ablate the expression of decidualization markers in DUS cells (e.g., PGR, PRLR, IGF1 or PTGES). In order to study the mechanisms involved in feto-maternal communication during pregnancy and induction of parturition, the goal of the present work was to assess transcriptional changes mediated by decidualization and antigestagens-induced effects in decidualized DUS cells. Decidualization led to the upregulation of 1841 differentially expressed genes (DEGs, P < 0.01, FDR < 0.01) involved in cellular proliferation and adhesion, mesenchymal-epithelial transition, extracellular matrix organization, and vaso- and immunomodulation. The 1475 DEGs downregulated after decidualization were mostly associated with apoptosis and cell migration. In decidualized DUS cells, aglepristone modulated 1400 DEGs and mifepristone 1558 DEGs. Interestingly, only around half of the identified DEGs were modulated uniquely by one of the antigestagens. In both situations, however, PGR-blockage was associated with an inversion of decidualization-induced effects. Comparison between antigestagens-mediated effects and transcriptional changes in the canine placenta at term allowed the identification of 191 DEGs associated with cell proliferation and adhesion, vascularization and immune activity. These findings emphasize the importance of P4/PGR signaling for decidual cells function.
2022-12-28 | GSE213788 | GEO
Project description:Decidualization is one of the most important processes during female reproduction, decidualization was regulated differently in first and subsequent pregnancies Notch1 affects decidualization of mouse uterine stromal cells, but the mechanisum under is still unclear
2021-03-24 | GSE153964 | GEO
Project description:Overactivation of notch1 signaling in uterine epithelium
| PRJNA851759 | ENA
Project description:The secretion of mammalian Wnt Ligands within the cell is dependent on the activity of Porcupine, a gene located on the X chromosome that encodes for a membrane bound o-acyl transferase. Porcupine-dependent Wnt signalling was previously shown to be essential for the post-natal maintenance of endometrial glands, structures that are essential for implantation and fertility. Previous data has implicated the multiple members of the Wnt family expressed in the female uterus to be involved in a coordinated crosstalk between the luminal and stromal compartments of the uterus, ensuring the proper development of the uterus and successful fertility. We have generated a conditional mutant of Porcupine in the luminal epithelium (cKOepi) of the uterus, thus eliminating Wnt7a/b and Wnt11, to address the nature of this crosstalk. Unlike global luminal-stromal mutants, post-natal ablation of Porcupine in the luminal epithelium alone does not affect the maintenance of the endometrial glands in adults. Uterine glands are still visible in the adult cKOepi, albeit in a smaller number than that of control uteri. Despite having uterine glands, cKOepi females remain completely infertile. We have attributed the sterility of these females to be in part due to defects in implantation and decidualization; cKOepi fail to respond to decidual induction by artificial means. Interestingly, progesterone supplementation rescues the observed implantation defects, although observed decidual soon seem to become resorptive. Microarray analysis of cKOepi during implantation has reveals several potential targets for luminal WNT that may be responsible for the observed phenotype including: Lef1, Hoxa10, Wnt4, Wnt16 Notch1, Notch4 and Dll4 .
2017-03-21 | GSE96801 | GEO
Project description:Regulatory T (Treg) cells are essential for maternal immune tolerance of the fetus and placenta. In preeclampsia, aberrant Treg cell tolerance is implicated, but whether and how Treg cells affect the uterine vascular dysfunction thought to precede placental impairment and maternal vasculopathy is unclear. We utilized Foxp3 DTR mice to test the hypothesis that Treg cells are essential regulators of decidual spiral artery adaptation to pregnancy. Transient Treg cell depletion during early placental morphogenesis caused impaired remodeling of decidual spiral arteries and altered uterine artery function, resulting in late gestation fetal loss and fetal growth restriction. Treg cell depletion impaired acquisition of the activation receptor NKp46 on uterine natural killer (uNK cells) and was associated with reduced decidual synthesis of Treg cell-derived cytokines Il35, Il10 and Tgfb implicated in modulating uNK cell phenotype. When Treg cells were replaced, the adverse impact on uNK cell abundance and phenotype, decidual spiral artery remodeling, uterine artery function, and fetal loss was mitigated. These data implicate Treg cells as essential upstream drivers of uterine vascular adaptation to pregnancy through regulation of uNK cell recruitment and activation. The findings provide a mechanism linking impaired adaptive immune tolerance and altered spiral artery remodeling, two hallmark features of preeclampsia.
2024-12-11 | GSE267364 | GEO
Project description:Our findings establish a key role for the coregulator, Repressor of Estrogen receptor Activity (REA), in controlling the timing and magnitude of decidualization in human endometrial stromal cells in vitro and in the mouse uterus in vivo, and suggest that REA functions to synchronize uterine differentiation with concurrent embryo development, which is essential for optimal implantation and fertility. The findings highlight that REA physiologically restrains endometrial stromal cell decidualization, controlling the timing and magnitude of decidualization to enable proper synchronization of uterine differentiation with concurrent embryo development that is essential for implantation and optimal fertility.
2013-04-04 | GSE42376 | GEO