Foxl2 mediated expression data from KK1 granulosa cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE18891 | GEO | 2009/11/05
SECONDARY ACCESSION(S): PRJNA121291
REPOSITORIES: GEO
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Project description:The Foxl2 transcription factor is required for ovarian function during follicular development. Our approach to begin to understand Foxl2 function is through the identification of Foxl2 regulated genes in the ovary. Transiently transfected KK1 mouse granulosa cells were used to identify genes that are potentially regulated by Foxl2. KK1 cells were transfected in three groups (mock, activated, and repressed) and twenty-four hours later RNA was isolated and submitted for Affymetrix microarray analysis. Experiment Overall Design: To increase the potential of Foxl2 to alter gene expression levels of putative target genes, two fusions were constructed consisting of Foxl2 fused to the activation domain of the Herpes simplex virus VP16 transcription factor (Foxl2-VP16) and Foxl2 fused to the repression domain of the murine MAD transcription factor (Foxl2-MAD). Levels of gene expression were compared between mock transfected cells and those that were transfected with Foxl2-VP16 and Foxl2-MAD, respectively.
2009-11-15 | E-GEOD-18891 | biostudies-arrayexpress
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
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, with mutants developing dysgenic ovaries devoid of oocytes. However, deletion of the gene in 8-week-old females leads to granulosa to Sertoli cell transdifferentiation and gonadal sex reversal. We hypothesise that different outcomes of Foxl2 deletion in embryonic versus adult ovary may depend on a different role played by FOXL2 across ovarian development. Therefore, in this study, we take a multi-omics approach to characterise 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 coupled these analyses with genome wide identification of FOXL2 target genes and on-chromatin interacting partners by ChIP-SICAP to reconstruct the gene regulatory networks underpinned by this essential transcription factor and to discover novel players. We found that, in the embryonic ovary, FOXL2 interacts with factors important for early stages of gonadal development, such as GATA4 and WT1, whilst postnatally it interacts with factors regulating primordial follicle activation, such as NR5A2, and with factors regulating steroidogenesis including AR and ESR2. Integration of chromatin landscape dynamics with gene expression changes and FOXL2 binding sites analysis revealed that its critical role in ovarian cell fate maintenance goes beyond repression of the Sertoli-specific gene Sox9. Our chromatome analysis revealed also that FOXL2 interacts with several proteins involved in chromatin remodelling, DNA repair, splicing and gene repression. We identified a FOXL2 interactor with a role in primordial follicle activation, Ubiquitin specific protease 7 (USP7). We showed that conditional deletion of this gene in granulosa cells leads to a blockage of primordial follicle activation, impairs ovary development and leads to complete sterility. In summary, in this study we identified target genes dynamically regulated by FOXL2 across ovarian development including known and newly identified FOXL2 targets with a role in embryonic ovarian development and folliculogenesis, as well as cofactors that point towards additional roles played by FOXL2 besides transcriptional regulation. This work constitutes a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.
2024-03-24 | GSE236860 | GEO
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, with mutants developing dysgenic ovaries devoid of oocytes. However, deletion of the gene in 8-week-old females leads to granulosa to Sertoli cell transdifferentiation and gonadal sex reversal. We hypothesise that different outcomes of Foxl2 deletion in embryonic versus adult ovary may depend on a different role played by FOXL2 across ovarian development. Therefore, in this study, we take a multi-omics approach to characterise 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 coupled these analyses with genome wide identification of FOXL2 target genes and on-chromatin interacting partners by ChIP-SICAP to reconstruct the gene regulatory networks underpinned by this essential transcription factor and to discover novel players. We found that, in the embryonic ovary, FOXL2 interacts with factors important for early stages of gonadal development, such as GATA4 and WT1, whilst postnatally it interacts with factors regulating primordial follicle activation, such as NR5A2, and with factors regulating steroidogenesis including AR and ESR2. Integration of chromatin landscape dynamics with gene expression changes and FOXL2 binding sites analysis revealed that its critical role in ovarian cell fate maintenance goes beyond repression of the Sertoli-specific gene Sox9. Our chromatome analysis revealed also that FOXL2 interacts with several proteins involved in chromatin remodelling, DNA repair, splicing and gene repression. We identified a FOXL2 interactor with a role in primordial follicle activation, Ubiquitin specific protease 7 (USP7). We showed that conditional deletion of this gene in granulosa cells leads to a blockage of primordial follicle activation, impairs ovary development and leads to complete sterility. In summary, in this study we identified target genes dynamically regulated by FOXL2 across ovarian development including known and newly identified FOXL2 targets with a role in embryonic ovarian development and folliculogenesis, as well as cofactors that point towards additional roles played by FOXL2 besides transcriptional regulation. This work constitutes a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.
2024-03-24 | GSE236859 | GEO
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, with mutants developing dysgenic ovaries devoid of oocytes. However, deletion of the gene in 8-week-old females leads to granulosa to Sertoli cell transdifferentiation and gonadal sex reversal. We hypothesise that different outcomes of Foxl2 deletion in embryonic versus adult ovary may depend on a different role played by FOXL2 across ovarian development. Therefore, in this study, we take a multi-omics approach to characterise 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 coupled these analyses with genome wide identification of FOXL2 target genes and on-chromatin interacting partners by ChIP-SICAP to reconstruct the gene regulatory networks underpinned by this essential transcription factor and to discover novel players. We found that, in the embryonic ovary, FOXL2 interacts with factors important for early stages of gonadal development, such as GATA4 and WT1, whilst postnatally it interacts with factors regulating primordial follicle activation, such as NR5A2, and with factors regulating steroidogenesis including AR and ESR2. Integration of chromatin landscape dynamics with gene expression changes and FOXL2 binding sites analysis revealed that its critical role in ovarian cell fate maintenance goes beyond repression of the Sertoli-specific gene Sox9. Our chromatome analysis revealed also that FOXL2 interacts with several proteins involved in chromatin remodelling, DNA repair, splicing and gene repression. We identified a FOXL2 interactor with a role in primordial follicle activation, Ubiquitin specific protease 7 (USP7). We showed that conditional deletion of this gene in granulosa cells leads to a blockage of primordial follicle activation, impairs ovary development and leads to complete sterility. In summary, in this study we identified target genes dynamically regulated by FOXL2 across ovarian development including known and newly identified FOXL2 targets with a role in embryonic ovarian development and folliculogenesis, as well as cofactors that point towards additional roles played by FOXL2 besides transcriptional regulation. This work constitutes a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.
2024-03-24 | GSE236785 | GEO
Project description:In order to identify genes misregulated by the adult OGCT-associated FOXL2 p.C134ZW mutant in granulosa cells, we have transfected COV434 cells (negative for the mutation) using an expression vector containing the wildtype or mutant coding sequence of FOXL2 or, as a reference, the empty vector pcDNA. The transcriptome perturbation induced by FOXL2 overexpression was then followed by DNA microarray using a platform developed by NimbleGen Systems, Inc.
2013-03-06 | E-MTAB-1017 | biostudies-arrayexpress
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
Project description:Foxl2 is a forkhead transcription factor essential for proper reproductive function in females. It is expressed in the somatic cell population of the gonad (granulosa cells) which forms the follicles of the ovary, the structures responsible for embedding and nurturing the oocytes during their development. FOXL2 directly regulate the aromatase that synthesizes estrogens CYP19A1, thus promoting female differentiation, as well as acting as a repressor of the male factors SOX9 and DMRT1.Expression is also found in the eyelids, pituitary gland and uterus. In the goat, frog and many fish species FOXL2 is a sex-determining gene which, when deleted, leads to female-to-male sex reversal.
2022-07-11 | PXD024439 | Pride
Project description:We discovered that expression of the transcription factor RUNX1 is enriched in the fetal ovary in various vertebrate species. In the mouse, RUNX1 marks the supporting cell lineage and becomes granulosa cell-specific as the gonads differentiate. To understand the function of Runx1 during fetal development of the ovary, we ablated Runx1 specifically in the somatic cell lineage of the fetal ovaries using Sf1-Cre . We compared ovarian differentiation in wild type, Runx1 and Foxl2 single knockouts, and Runx1/Foxl2 double knockout ovaries. Transcriptome comparisons of newborn ovaries revealed that loss of Runx1 or Foxl2 affected a similar set of genes: 41% of the genes affected by the loss of Runx1 were also changed by the loss of Foxl2. Despite these transcriptomic changes, granulosa cell identity was maintained during fetal life in both Runx1 or Foxl2 single knockout ovaries. However, the combined loss of Runx1/Foxl2 resulted in masculinization of the ovaries during fetal life. To further characterize the impacts of the combined loss of Runx1 and Foxl2 on ovarian differentiation, we compared the transcriptome of Runx1/Foxl2 DKO newborn ovaries with the transcriptomes of control, Runx1, or Foxl2 single KO ovaries.
2019-07-17 | GSE129038 | GEO
Project description:We have generated a humanized Foxl2 mouse model by genome editing to evaluate in vivo the role of mutated FOXL2 in the development of murine Adult Granulosa Cell Tumors
2023-01-31 | GSE202242 | GEO