Similar Datasets
Project description:Mouse ovarian P2 dataset for the protein atlas of ovarian aging
| PRJNA993403 | ENA
Project description:Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates (NHPs) and identified seven ovarian cell types with distinct gene expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species and apoptosis were observed in granulosa cells from aged women. This study provides comprehensive understanding of the cell type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.
2020-01-28 | GSE130664 | GEO
Project description:Single-Cell Transcriptomic Atlas of Primate Ovarian Aging
| PRJNA540933 | ENA
Project description:BackgroundThe ovaries are one of the first organs that undergo degenerative changes earlier in the aging process, and ovarian aging is shown by a decrease in the number and quality of oocytes. However, little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging, especially in goats. Therefore, the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell resolution.ResultsFor the first time, we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn, young and aging goats, and identified nine ovarian cell types with distinct gene-expression signatures. Functional enrichment analysis showed that ovarian cell types were involved in their own unique biological processes, such as Wnt beta-catenin signalling was enriched in germ cells, whereas ovarian steroidogenesis was enriched in granulosa cells (GCs). Further analysis showed that ovarian aging was linked to GCs-specific changes in the antioxidant system, oxidative phosphorylation, and apoptosis. Subsequently, we identified a series of dynamic genes, such as AMH, CRABP2, THBS1 and TIMP1, which determined the fate of GCs. Additionally, FOXO1, SOX4, and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian aging.ConclusionsThis study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell type-specific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases.
| S-EPMC10699009 | biostudies-literature
Project description:Ovarian aging leads to diminished fertility, dysregulated endocrine signaling, and increased chronic disease burden. These effects begin to emerge long before follicular exhaustion. Around 35 years old, women experience a sharp decline in fertility, corresponding to declines in oocyte quality. However, the field lacks a cellular map of the transcriptomic changes in the aging ovary to identify drivers of ovarian decline. To fill this gap, we performed single-cell RNA sequencing on ovarian tissue from young (3-month-old) and reproductively aged (9-month-old) mice. Our analysis revealed a doubling of immune cells in the aged ovary, with T and B lymphocyte proportions increasing most. We also discovered an age-related upregulation of alternative macrophage and downregulation of collagenase pathways in stromal fibroblasts. Overall, follicular cells (especially granulosa and theca) display stress response, immunogenic, and fibrotic signaling pathway inductions with aging. These changes are more exaggerated in the atretic granulosa cells but are also observed in healthy antral and preantral granulosa cells. Moreover, we did not observe age-related changes in markers of cellular senescence in any cellular population with advancing age, despite specific immune cells expressing senescence-related genes across both timepoints. This report raises several new hypotheses that could be pursued to elucidate mechanisms responsible for ovarian aging phenotypes.
2023-11-27 | GSE232309 | GEO
Project description:Background. Genome-wide expression changes are associated with development of chemoresistance in patients with ovarian cancer (OVCA); the BCL2 antagonist of cell death (BAD) apoptosis pathway may play a role in clinical outcome. Methods. We analyzed specimens and/or genomic data from 1,406 patients and 116 cancer cell lines. Genome-wide expression changes and cisplatin-resistance were evaluated in OVCA cell lines subjected to a total of 144 (cisplatin)-treatment/recovery cycles. Pathway analysis was performed on genes associated with increasing cisplatin-resistance. BAD protein phosphorylation was studied in patient samples and cell lines, and small interfering RNAs (siRNA) used to explore the pathway as a therapeutic target. We evaluated the influence of BAD-pathway expression on chemosensitivity and/or clinical outcome using genomic data from 60 human cancer cell lines and ovarian, breast, colon, and brain cancers from 1,258 patients. Results. The BAD pathway was associated with evolution of OVCA cell line cisplatin-resistance (P<0.001) and resistance of 7 human cancer cell types to 8 cytotoxic agents (P<0.05). OVCA chemoresistance was associated with BAD protein phosphorylation, and targeted siRNA modulation produced corresponding changes in chemosensitivity. Expression of a 47-gene BAD-pathway signature was associated with survival of 1,258 patients with ovarian, breast, colon, and brain cancer. The OVCA BAD-pathway signature survival advantage was independent of surgical cytoreductive status. Conclusions. The BAD apoptosis pathway influences the sensitivity of human cancers to a variety of chemotherapies, likely via modulation of BAD-phosphorylation. The pathway has clinical relevance as a potential biomarker of therapeutic response, patient survival, and as a promising therapeutic target. Twenty-eight (28) advanced-stage serous epithelial ovarian cancers were resected at the time of primary surgery from patients who would receive platinum-based therapy. The tumors were arrayed on Affymetrix HG-U133A GeneChips. The samples were analyzed with respect to the BAD pathway for correlation to overall survival and cisplatin response.
2011-10-02 | E-GEOD-23554 | biostudies-arrayexpress
Project description:Background. Genome-wide expression changes are associated with development of chemoresistance in patients with ovarian cancer (OVCA); the BCL2 antagonist of cell death (BAD) apoptosis pathway may play a role in clinical outcome. Methods. We analyzed specimens and/or genomic data from 1,406 patients and 116 cancer cell lines. Genome-wide expression changes and cisplatin-resistance were evaluated in OVCA cell lines subjected to a total of 144 (cisplatin)-treatment/recovery cycles. Pathway analysis was performed on genes associated with increasing cisplatin-resistance. BAD protein phosphorylation was studied in patient samples and cell lines, and small interfering RNAs (siRNA) used to explore the pathway as a therapeutic target. We evaluated the influence of BAD-pathway expression on chemosensitivity and/or clinical outcome using genomic data from 60 human cancer cell lines and ovarian, breast, colon, and brain cancers from 1,258 patients. Results. The BAD pathway was associated with evolution of OVCA cell line cisplatin-resistance (P<0.001) and resistance of 7 human cancer cell types to 8 cytotoxic agents (P<0.05). OVCA chemoresistance was associated with BAD protein phosphorylation, and targeted siRNA modulation produced corresponding changes in chemosensitivity. Expression of a 47-gene BAD-pathway signature was associated with survival of 1,258 patients with ovarian, breast, colon, and brain cancer. The OVCA BAD-pathway signature survival advantage was independent of surgical cytoreductive status. Conclusions. The BAD apoptosis pathway influences the sensitivity of human cancers to a variety of chemotherapies, likely via modulation of BAD-phosphorylation. The pathway has clinical relevance as a potential biomarker of therapeutic response, patient survival, and as a promising therapeutic target.
2011-10-03 | GSE23554 | GEO
Project description:Ovarian aging is characterized by the progressive depletion of primordial follicle reserve, leading to irregular patterns of ovulation and menopause. The basic mechanisms that underlie the ovarian aging and follicle decline is unknown. We sought to explore the role of cellular senescence and epigenomic mechanisms in ovarian aging. Here, we present the transcriptomic changes observed in the ovaries with age using the age groups 3mo, 6mo, 9mo and 12mo (n=5 per group except for 12mo which has an n=4). The age groups capture timepoints from sexual maturation to reproductive health decline.
2020-07-23 | GSE154890 | GEO
Project description:Chromatin Proteome was enriched from drosophila ovarian somatic cells using ChEP.
2021-07-02 | PXD024167 | JPOST Repository
Project description:We present a meta-dataset comprising of a total of 663 samples including both primary tumors and tumor-free ovarian tissues from ten independent GEO datasets. To minimise inter-platform variation, only datasets generated from the GPL570 platform (Affymetrix Human Genome U133 Plus 2.0 Array) were processed to develop the meta-dataset. Using multiple open source R packages implemented in our previously developed bioinformatics pipeline, each dataset has been preprocessed with RMA normalisation, merged, and batch effect-corrected via Combat method. With increased sample size, the present meta-dataset serves an excellent 'discovery cohort' for discovering differentially expressed in diseased phenotype.
2019-04-11 | E-MTAB-6691 | biostudies-arrayexpress