RNA-seq of ME-HESC in SRF-deficient vs Normal Conditions
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE292411 | GEO | 2025/09/30
REPOSITORIES: GEO
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Project description:The transcription factor SRF plays known roles in mitogenic cell response and muscle cell development, and potential roles in endometrial stromal decidualization have been reported. After RNAi-based SRF knockdown in hTERT-immortalized human endometrial stromal cells (THESC), SRF-deficient cells exhibited disrupted cytoskeletal remodeling, cell cycle, and extracellular matrix genes. These data show that SRF is important for endometrial stromal cell homeostasis.
2025-09-30 | GSE292415 | 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:Uterine glands and, by inference, their secretions impact uterine receptivity, blastocyst implantation, stromal cell decidualization, and placental development. Changes in gland function across the menstrual cycle are impacted by steroid hormones, estrogen and progesterone, as well as stroma-derived factors. Using an endometrial epithelial organoid (EEO) system, transcriptome and proteome analyses identified distinct responses of the EEO to steroid hormones and prostaglandin E2 (PGE2). Notably, steroid hormones and PGE2 modulated the basolateral secretion of EEO proteins, where cystatin C (CST3) was significantly increased by progesterone and PGE2. CST3 treatment of decidualizing stromal cells significantly decreased the decidualization markers PRL and IGFBP1. The attenuation of stromal cell decidualization via CST3 suggests a role for uterine gland-derived proteins in controlling the extent of decidualization. These findings provide evidence that uterine gland-derived factors directly impact stromal cell decidualization, which has strong implications for better understanding pregnancy establishment and female fertility in humans.
2023-10-11 | PXD034357 | Pride
Project description:Cellular senescence leads to stable cell cycle arrest and an inflammatory senescence-associated secretory phenotype that varies with stressor and cell type. To mitigate these effects and improve health, senotherapeutics (e.g., senolytics and senomorphics) have been developed. Senescent-like endometrial stromal cells (eSCs) lining the uterus of patients with endometriosis and infertility are proposed to impair decidualization, a differentiation process required for uterine receptivity in humans. Quercetin, a natural flavonoid senolytic, dramatically improves decidualization and reduces endometriosis in rodent models. However, little is known about the comparative effects of various senotherapeutics on eSCs. Using menstrual effluent-derived eSCs, we evaluated the effects of flavonoid and non-flavonoid compounds on eSC functions associated with endometriosis, aiming to identify optimal senotherapeutics for future clinical trials. Among flavonoids tested, all senolytics (quercetin, fisetin, and luteolin) and kaempferol, a senomorphic, significantly improved decidualization without cytotoxicity. Although non-flavonoids exhibited notable cytotoxicity, dasatinib, but neither ABT-737 nor navitoclax, enhanced decidualization. Flavonoid senotherapeutics and dasatinib significantly inhibited eSC migration. Mechanistic studies revealed that all flavonoids and dasatinib suppressed AKT phosphorylation and upregulated p53 expression. Notably, only quercetin and fisetin reduced ERK1/2 phosphorylation. Furthermore, flavonoid-senolytics and dasatinib consistently eliminated senescent eSCs. These findings support future studies to assess the therapeutic potential of in vivo supplementation with flavonoid senolytics on eSC function using menstrual effluent.
2025-07-02 | GSE299492 | GEO
Project description:Decidualization of human endometrial stromal cells (hESCs), a critical process for embryo implantation and successful pregnancy, begins during the secretory phase of the menstrual cycle. We evaluated 25 established in vitro decidualization markers in hESCs using in vivo single-cell transcriptomic data. Most markers, including PRL and IGFBP1, did not reliably distinguish between proliferative and secretory phase hESCs, nor between decidualized and non-decidualized hESCs. Only 8 genes (STAT3, CEBPB, WNT4, IL-15, TIMP3, HAND2, FOXO1 and MMP19) showed differential expression between the menstrual phase and decidualization status in vivo. We hypothesized that the difference between in vitro and in vivo marker expression might result from the absence of endometrial glands in the in vitro decidualization model. While endometrial glands are known to secrete factors critical for uterine receptivity, their specific role in decidualization is not well understood. To investigate this, we examined the influence of the glandular secretome on ESC decidualization using an in vitro co-culture model of human endometrial organoids (hEOs) and hESCs. Decidualization was induced in hESCs, and the effects of hEO co-culture or exposure to hEO secretome were assessed by morphological analysis, molecular marker expression, and transcriptomic profiling. Unexpectedly, both hEO co-culture and exposure to the hEO secretome significantly reduce the up-regulation of canonical decidualization markers and the mesenchymal-epithelial transition typically induced during hESC decidualization. Transcriptomic analysis further revealed downregulation of decidualization regulators, CEBPA and EDN1, in ESCs exposed to the hEO secretome compared to decidualized controls. These findings were corroborated in an estradiol-stimulated mouse model, where increased endometrial gland formation correlated with reduced decidualization and lower expression of CEBPA and EDN1. Collectively, our results reveal a previously unrecognized homeostatic role for the endometrial gland secretome in regulating ESC decidualization. These insights highlight the limitations of current in vitro decidualization models and underscore the importance of glandular-stromal interactions in endometrial function and reproductive health.
2025-08-05 | GSE303741 | GEO
Project description:Uterine glands and, by inference, their secretions impact uterine receptivity, blastocyst implantation, stromal cell decidualization, and placental development. Changes in gland function across the menstrual cycle are impacted by steroid hormones, estrogen and progesterone, as well as stroma-derived factors. Using an endometrial epithelial organoid (EEO) system, transcriptome and proteome analyses identified distinct responses of the EEO to steroid hormones and prostaglandin E2 (PGE2). Notably, steroid hormones and PGE2 modulated the basolateral secretion of EEO proteins, where cystatin C (CST3) was significantly increased by progesterone and PGE2. CST3 treatment of decidualizing stromal cells significantly decreased the decidualization markers PRL and IGFBP1. The attenuation of stromal cell decidualization via CST3 suggests a role for uterine gland-derived proteins in controlling the extent of decidualization. These findings provide evidence that uterine gland-derived factors directly impact stromal cell decidualization, which has strong implications for better understanding pregnancy establishment and female fertility in humans.
2022-06-06 | GSE205084 | GEO
Project description:We report the genome-wide binding sites of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells that express either PGR-A or PGR-B. Progesterone, acting through the progesterone receptors (PGRs), is one of the most critical regulators of endometrial differentiation, known as decidualization, which is a key step toward the establishment of pregnancy. Yet a long-standing unresolved issue in uterine biology is the precise roles played by the major PGR isoforms, PGR-A and PGR-B, during decidualization in the human. Our approach, expressing PGR-A and PGR-B individually after silencing endogenous PGRs in human endometrial stromal cells (HESC), enabled the analysis of the roles of these isoforms separately as well as jointly by ChIP-seq and gene-expression analysis. In order to study the cistromes of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells, we generated primary cultures of human endometrial stromal cells expressing flag tagged PGR-A and PGR-B individually after silencing endogenous PGRs. Input DNA was used as the reference sample.
2015-04-27 | E-GEOD-62475 | biostudies-arrayexpress
Project description:Menstrual effluent cell profiles have potential as noninvasive biomarkers of female reproductive and gynecological health and disease. We used DNA methylation-based cell type deconvolution (methylation cytometry) to identify cell type profiles in self-collected menstrual effluent. During the second day of their menstrual cycle healthy participants collected menstrual effluent using a vaginal swab, menstrual cup, and pad. Immune cell proportions were highest in menstrual cup samples, and epithelial cells were highest in swab samples. Our work demonstrates the feasibility and utility of menstrual effluent cell profiling in population-level research using remotely collected samples and DNA methylation.
2025-08-01 | GSE275888 | GEO
Project description:Wilms tumor 1 (WT1) regulates the expression of insulin-like growth factor-binding protein-1 (IGFBP-1) and prolactin (PRL) during decidualization of human endometrial stromal cells (ESCs). However, other roles of WT1 in decidualization have not been fully clarified. We used microarrays to identify the physiological roles of WT1 in the regulation of cellular functions of human ESCs during decidualization.
2020-02-25 | GSE136616 | GEO
Project description:Background. Endometriosis is a common, complex disorder which is underrecognized and subject to prolonged delays in diagnosis. It is accompanied by significant changes in the eutopic endometrial lining. Methods . We have undertaken the first single cell RNA-sequencing (scRNA-Seq) comparison of endometrial tissues in freshly collected menstrual effluent (ME) from 33 subjects, including confirmed endometriosis patients (cases) and controls as well as symptomatic subjects (who have chronic symptoms of endometriosis but have not been diagnosed). Results . We identify a unique subcluster of proliferating uterine natural killer (uNK) cells in ME-tissues from controls that is almost absent from endometriosis cases, along with a striking reduction of total uNK cells in the ME of cases (p<10 -16 ). In addition, an IGFBP1+ decidualized subset of endometrial stromal cells are abundant in the shed endometrium of controls when compared to cases (p<10 -16 ) confirming findings of compromised decidualization of cultured stromal cells from cases. By contrast, endometrial stromal cells from cases are enriched in cells expressing pro-inflammatory and senescent phenotypes. An enrichment of B cells in the cases (p=5.8 x 10 -6 ) raises the possibility that some may have chronic endometritis, a disorder which predisposes to endometriosis. Conclusions . We propose that characterization of endometrial tissues in ME will provide an effective screening tool for identifying endometriosis in patients with chronic symptoms suggestive of this disorder. This constitutes a major advance, since delayed diagnosis for many years is a major clinical problem in the evaluation of these patients. Comprehensive analysis of ME is expected to lead to new diagnostic and therapeutic approaches to endometriosis and other associated reproductive disorders such as female infertility.
2022-09-21 | GSE203191 | GEO