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ABSTRACT: Whole genome transcriptomic analysis of ovary granulosa cells

PROVIDER: PRJNA787430 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17425237_1.fastq.gz	Fastqsanger.gz
	SRR17425237_2.fastq.gz	Fastqsanger.gz
	SRR17425238_1.fastq.gz	Fastqsanger.gz
	SRR17425238_2.fastq.gz	Fastqsanger.gz
	SRR17425239_1.fastq.gz	Fastqsanger.gz

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Genome wide identification of FOXL2 binding sites in mouse fetal ovaries

Project description:The identity of the gonads is determined by which fate, ovarian granulosa cell or testicular Sertoli cell, the bipotential somatic cell precursors choose to follow. In most vertebrates, the fate of granulosa cells is controlled by a conserved regulator FOXL2. To understand how FOXL2 elicits its fate-determining action, we performed genome-wide analysis of FOXL2 chromatin occupancy in fetal ovaries. Combining genome-wide analysis of FOXL2 binding in the fetal ovary with transcriptomic analyses of Foxl2 gain-of-function and Foxl2 loss-of-function models, we identified potential pathways responsible for the feminizing action of FOXL2. Finally, comparison of FOXL2 genome-wide occupancy in the fetal ovary with testis-determining factor SOX9 genome-wide occupancy in the fetal testis revealed extensive overlaps, implying that antagonistic signals between FOXL2 and SOX9 occur at the chromatin level.

2019-03-21 | GSE110093 | GEO

FOXL2 interaction with different binding partners regulates the dynamics of granulosa cell differentiation across ovarian development

Project description:FOXL2 is a transcription factor essential for female fertility, expressed in somatic cells of the ovary, notably granulosa cells. In the mouse, Foxl2 deletion leads to partial sex reversal postnatally. However, deletion of the gene in 8-week-old females leads to granulosa to Sertoli cell transdifferentiation. We hypothesised that different outcomes of Foxl2 deletion in embryonic versus adult ovary may depend on a different role played across ovarian development. Therefore, we characterised the dynamics of gene expression and chromatin accessibility changes in purified murine granulosa cells across key developmental stages (E14.5, 1 and 8 weeks). We then performed genome-wide identification of FOXL2 target genes and on-chromatin interacting partners by ChIP-SICAP. We found that FOXL2 regulates more genes at postnatal stages, through the interaction with factors regulating primordial follicle activation (PFA), such as NR5A2, and others regulating steroidogenesis including AR and ESR2. As a proof of principle experiment, we chose one FOXL2 interactor, Ubiquitin specific protease 7 (USP7) and showed that deletion of this gene in granulosa cells leads to a blockage of PFA, impaired ovary development and sterility. Our study constitutes a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.

2024-03-25 | PXD043951 | Pride

Dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis

Project description:Ovarian follicle development is a complex and well-orchestrated biological process. Granulosa cells (GCs) are the most important somatic cells in the ovary, which play important roles in the growth of follicles. Three-dimensional (3D) chromatin architecture has emerged as an important regulator of transcription in eukaryote, but how these changes in granulosa cells during folliculogenesis of chicken are largely unexplored. Here, we performed an integrative analysis of transcriptomic and chromatin structural characterization for chicken follicular granulosa cells of 10 and 3 growth stages respectively.

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Neurotensin expressed in the granulosa cells regulates selective genes that are potentially involved in the ovulatory process

Project description:Neurotensin (NTS) is a small 13 amino acid neuropeptide. In the mouse ovary, the expression of Nts ovary increases 250-fold 4h after hCG. Similarly, in granulosa cells, the mRNA levels of Nts increased rapidly at 4h after hCG stimulation. Interestingly, the Nts mRNA levels in granulosa cells were approximately 8-fold higher at 4 h after hCG than in whole ovaries. However, the potential mechanisms of NTS action in the ovulatory process are unknown. The present study determined the regulatory mechanisms driving the expression of Nts and functions of the NTS using primary mouse granulosa cells. hCG activated PKA and p38MAPK signaling pathways, and inhibitors for these pathways abolished hCG-induced increases in the levels of Nts. To identify the genes regulated by NTS, high throughput RNA sequencing was performed using Nts silenced mouse granulosa cells treated with or without hCG. Sequencing data analysis revealed that Nts knockdown affects the expression of several genes that were not previously identified in the ovary. qPCR analysis verified hCG-induced, Nts-regulated expression of a selection of these genes. This study revealed novel genes regulated by NTS, thereby providing a function for NTS in the ovulatory process.

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Whole genomic DNA methylation analysis across human polycystic ovary syndrome ovary granulosa cells [MBD-seq]

Project description:Whole genomic DNA methylation analysis across human polycystic ovary syndrome ovary granulosa cells [MBD-seq]

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Project description:ERβ is predominantly expressed in granulosa cells of the ovary, where its important for normal ovarian function and plays a vital role in folliculogenesis. However, the genome wide binding landscape of ERβ in the ovary was not determined and its interaction targets are unknown. To characterize the mechanism of ERβ, we performed ChIP-Seq using endogenous ERβ expression and mapped the cistrome of ERβ in the ovary using a validated antibody.

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Androgens Regulate Ovarian Gene Expression through Modulation of H3K27me3 in Granulosa Cells [ChIP-seq]

Project description:This study reports androgen-induced gene expression in granulosa cells of the ovary and provides a molecular insight of how androgens regulate granulosa cell gene expression through modulating the epigenetic mark H3K27me3.

2020-06-19 | GSE152791 | GEO

CRISPR targeting of FOXL2 c.402C>G mutation reduces malignant phenotype in granulosa tumor cells and identifies anti-tumoral compounds

Project description:FOXL2 is a transcription factor that plays a key role in sex determination, ovary development and maintenance. Mutations related to this gene have been described in syndromes involving premature ovarian failure and granulosa cell tumors. This kind of rare cancer (less than 5% of diagnosed ovarian cancers) has been causally associated with the FOXL2 c.402C>G, p.C134W mutation in 97% of the adult cases (AGCTs). In this study, we have used CRISPR technology to specifically eliminate the FOXL2 c.402C>G mutation in granulosa tumor cells. Our results indicate that this Cas9-mediated strategy allows the specific elimination of the mutation with no activity on the wild type allele. Granulosa cells depleted on FOXL2 c.402C>G show a reduced malignant phenotype. Specifically, we detect changes in cell proliferation, invasion, and cell death levels. In addition, we show that granulosa tumor cells become more susceptible to Dasatinib and Ketoconazole treatments when FOXL2 c.402C>G allele is eliminated. Our transcriptomic and proteomic analyses indicate that CRISPR-modified granulosa tumor cells significantly change their expression signature towards a wild type like phenotype. Finally, this expression signature has led us to discover new compounds with antiproliferative and proapoptotic effects on granulosa cell tumor cells. Our results demonstrate the potential of CRISPR for specifically targeting and eliminating a granulosa cell tumor-causing mutation, as well as its therapeutic potential for the treatment of this rare ovarian cancer.

2025-03-15 | PXD053682 | Pride

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (ChIP-Seq 1)

Project description:We study the role of the protein Trim28 in the maintenance of sexual identity of the adult ovary. With the help of conditional knock out (cKO) of Trim28 using the Nr5a1:Cre, we observed that deletion of the Trim28 gene in granulosa cells of the adult ovary induces their transdifferentiation into Sertoli cells, the supporting cell lineage of the testicular seminiferous tubules. FOXL2 expression has disappeared and follicles were completely remodeled into tubular structures with cells that expressed the Sertoli cell markers SOX8, SOX9 and DMRT1. Histological analysis confirmed the progressive reorganization of ovarian follicles into tubular structures and the and the transdifferentiation of granulosa cells by cells with a Sertoli cell morphology.

2022-05-24 | GSE166383 | GEO

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