Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-26966
PROVIDER: PRJNA136983 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gonadotrope or null cell pituitary tumors present clinically with signs of hypogonadism and hypopituitarism, together with visual disturbances due to mass effects. Since there are no medical therapies, surgery and/or radiation are the only therapeutic options. To identify dysregulated genes and/or pathways that may play a role in tumorigenesis and/ or progression, molecular profiling was performed on 14 gonadotrope tumors and 9 normal human pituitaries from autopsy samples. Principle component analysis (PCA) revealed clear discrimination between tumor and normal pituitary gene expression profiles. Bioinformatic analysis identified specific genes and pathways that were highly differentially regulated, including a cohort of putative downstream effectors of p53 were repressed in gonadotrope pituitary tumors, including GADD45β, GADD45γ and Reprimo with concomitant downregulation of the upstream regulator, PLAGL1. PLAGL1 reexpression in gonadotrope cells did not directly modulate the downstream targets. Further functional analysis of GADD45β was performed. Overexpression of GADD45β in mouse gonadotrope cells blocked proliferation, increased rates of apoptosis in response to growth factor withdrawal and increased colony formation in soft agar. In contrast to prior studies with GADD45γ, methylation interference assays showed no evidence of epigenetic modification of the GADD45β promoter in pituitary tumors. Thus, our data suggest that many components downstream of p53 are suppressed in gonadotrope pituitary tumors. A novel candidate, GADD45β is low in tumors and reexpression blocks proliferation, survival and tumorigenesis in gonadotrope cells. Unlike GADD45γ, GADD45β is not methylated to block its expression. Together these studies identify new targets and mechanisms to explore concerning pituitary tumor initiation and progression. To elucidate mechanisms involved in pituitary tumorigenesis and progression, we performed individual gene expression microarray analysis using Affy U133 Plus 2.0 GeneChips comparing 14 gonadotrope tumors with 9 normal pituitary samples obtained at autopsy.
2011-01-31 | E-GEOD-26966 | biostudies-arrayexpress
Project description:Gonadotrope or null cell pituitary tumors present clinically with signs of hypogonadism and hypopituitarism, together with visual disturbances due to mass effects. Since there are no medical therapies, surgery and/or radiation are the only therapeutic options. To identify dysregulated genes and/or pathways that may play a role in tumorigenesis and/ or progression, molecular profiling was performed on 14 gonadotrope tumors and 9 normal human pituitaries from autopsy samples. Principle component analysis (PCA) revealed clear discrimination between tumor and normal pituitary gene expression profiles. Bioinformatic analysis identified specific genes and pathways that were highly differentially regulated, including a cohort of putative downstream effectors of p53 were repressed in gonadotrope pituitary tumors, including GADD45β, GADD45γ and Reprimo with concomitant downregulation of the upstream regulator, PLAGL1. PLAGL1 reexpression in gonadotrope cells did not directly modulate the downstream targets. Further functional analysis of GADD45β was performed. Overexpression of GADD45β in mouse gonadotrope cells blocked proliferation, increased rates of apoptosis in response to growth factor withdrawal and increased colony formation in soft agar. In contrast to prior studies with GADD45γ, methylation interference assays showed no evidence of epigenetic modification of the GADD45β promoter in pituitary tumors. Thus, our data suggest that many components downstream of p53 are suppressed in gonadotrope pituitary tumors. A novel candidate, GADD45β is low in tumors and reexpression blocks proliferation, survival and tumorigenesis in gonadotrope cells. Unlike GADD45γ, GADD45β is not methylated to block its expression. Together these studies identify new targets and mechanisms to explore concerning pituitary tumor initiation and progression.
2011-01-31 | GSE26966 | GEO
Project description:Proper expression of key reproductive hormones from gonadotrope cells of the pituitary is required for reproduction. We performed RNAseq of 3 maturaton staged gonadotrope cell lines, a thyroptrope cell line and NIH-3T3 cells to establish the timing and expression levels of genes involved in gonadotrope maturation.
2017-11-01 | GSE104513 | GEO
Project description:The growth arrest and DNA-damage induced 45 gamma (GADD45g) is rapidly induced by various physiological and environmental stresses associated with growth arrest. GADD45g has been observed implicated in cell survival, apoptosis, senescence, cell cycle regulation and DNA repair in a variety of human solid tumor types, acting as either tumor promoter or tumor suppressor. To date, the role of GADD45g in hematopoietic malignancies remains completely unknown. Here, we transduced Molm-13 cells with lentiviral vectors expressing doxycycline-inducible GADD45g. Molm-13 cells with dox administration or not were collected for RNA-seq.
2023-06-22 | GSE152932 | GEO
Project description:We report the single nucleus multiome (RNAseq+ATACseq) of a male mouse pituitary sample. This dataset was generated for supporting the development of a novel computational framework for analyzing gene regulatorty circuitry from single cell multiome datasets. This computational framework extract regulatory circuits consisting of TFs, cis-regulatory sites and target genes by modelling the co-incidence of the RNA levels of the TFs, the chomatin accessibility of the TFs' binding sites and the RNA levels of target genes across single cell. Specifically we identified gonadotrope-specific regulatory circuits under the transcription factor Gata2. These regulatory circuits were validated by male mouse pituitary samples with gonadotrope-conditional knockout of Gata2 previously reported in GSE190066.
2023-12-13 | GSE234943 | GEO
Project description:The goals of this study is to enrich the population of ovine gonadotropes via adenovirus-mediated targeting and flow cytometry to compare NGS-derived transcriptome profiling (RNA-seq) of a gonadotrope-enriched cell population to the combined transcriptome of all anterior pituitary cells and apply enrichment method to query the transcriptome of sorted ovine pituitary cells in response to treatment with 10 nM estradiol (E2) for six hours. Methods: mRNA profiles of sheep anterior pituitary cells were generated by deep sequencing, in sextuplicates, using Illumina HiSeq. The sequence reads that passed quality filters were analyzed at the transcript level with GSNAP, followed by featureCounts and then followed by edgeR. qRT–PCR validation was performed using SYBR Green assays. Results: About 124 million sequence reads per sample were mapped to the sheep genome (Oar v.3.1) which identified 17,082 transcripts in the pituitaries. RNA-seq data confirmed overrepresentation of genes known to be expressed in pituitary in sorted samples; 11 of genes (5 gonadotrope-specific and 6 non gonadotrope-specific) were validated with qRT–PCR. RNA-seq data had a linear relationship with qRT–PCR. Approximately 7.2% of the transcripts showed differential expression between the sorted (gonadotropes) and unsorted (all anterior pituitary cells) pituitary cells, with a fold change ≥3 and FDR <0.05. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to gonadotrope function. 232 genes were detected as upregulated in the sorted GFP-positive cells treated with E2 (gonadotropes) and 31 were downregulated following E2 treatment with a fold change ≥1.5 and FDR <0.1. Conclusions: Our study represents the first detailed analysis of the gonadotrope transcriptome, with 6 biologic replicates, generated by RNA-seq technology. The data analysis workflows reported here should provide a framework for comparative investigations of gonadotrope expression profiles. This method was applied to determine differentially expressed genes in the sorted population of pituitary cells (gonadotropes) in response to 10 nM E2.
2019-10-22 | GSE121685 | GEO
Project description:After DNA damage, cells activate p53, a tumor suppressor gene, and select a cell fate (e.g., DNA repair, cell cycle arrest, or apoptosis). Recently, a p53 oscillatory behavior was observed following DNA damage. However, the relationship between this p53 oscillation and cell-fate selection is unclear. Here, we present a novel model of the DNA damage signaling pathway that includes p53 and whole cell cycle regulation and explore the relationship between p53 oscillation and cell fate selection. The simulation run without DNA damage qualitatively realized experimentally observed data from several cell cycle regulators, indicating that our model was biologically appropriate. Moreover, the comprehensive sensitivity analysis for the proposed model was implemented by changing the values of all kinetic parameters, which revealed that the cell cycle regulation system based on the proposed model has robustness on a fluctuation of reaction rate in each process. Simulations run with four different intensities of DNA damage, i.e. Low-damage, Medium-damage, High-damage, and Excess-damage, realized cell cycle arrest in all cases. Low-damage, Medium-damage, High-damage, and Excess-damage corresponded to the DNA damage caused by 100, 200, 400, and 800 J/m(2) doses of UV-irradiation, respectively, based on expression of p21, which plays a crucial role in cell cycle arrest. In simulations run with High-damage and Excess-damage, the length of the cell cycle arrest was shortened despite the severe DNA damage, and p53 began to oscillate. Cells initiated apoptosis and were killed at 400 and 800 J/m(2) doses of UV-irradiation, corresponding to High-damage and Excess-damage, respectively. Therefore, our model indicated that the oscillatory mode of p53 profoundly affects cell fate selection.
2024-09-02 | BIOMD0000000939 | BioModels
Project description:Inhibition of leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) prevents the development of Mixed Lineage Leukemia (MLL)-arranged AML in mice and suppresses activation of Wnt/beta-catenin signaling. To identify key downstream targets of Lgr4, we performed genome-wide gene expression analysis. Our microarray analysis and subsequent in vivo studies demonstrate a novel functional role for growth arrest and DNA damage-inducible 45 (Gadd45a) in promoting in vivo self-renewal of leukemic stem cells in MLL-rearranged AML. GFP-positive leukemic cells flow-sorted by BD Influx cell sorter from bone marrow of primary AML mice induced by MLL-AF9 oncogene were lentivirally transduced with Lgr4 shRNA (MSH040504-3-LVRU6MP, GeneCopoeia) or Scrambled control (CSHCTR001-LVRU6MP, GeneCopoeia), and replated in methylcellulose supplemented with IL3. Each group contains triplicate samples.
2023-08-30 | E-MTAB-4773 | biostudies-arrayexpress
Project description:Follicle-stimulating hormone (FSH), a dimeric glycoprotein produced by pituitary gonadotrope cells, regulates spermatogenesis in males and ovarian follicle growth in females. Hypothalamic gonadotropin-releasing hormone (GnRH) stimulates FSHβ subunit gene (Fshb) transcription, though the underlying mechanisms are poorly understood. To address this gap in knowledge, we examined changes in pituitary gene expression in GnRH-deficient mice (hpg) treated with a regimen of exogenous GnRH that increases pituitary Fshb but not luteinizing hormone β (Lhb) mRNA levels. Activating transcription factor 3 (Atf3) was among the most upregulated genes. ATF3 can heterodimerize with members of the AP-1 family to regulate gene transcription. Co-expression of ATF3 with JunB stimulated murine Fshb, but not Lhb, promoter-reporter activity in homologous LβT2 cells. ATF3 also synergized with a constitutively active activin type I receptor to increase endogenous Fshb expression in these cells. Nevertheless, FSH production was intact in gonadotrope-specific Atf3 knockout mice (cKO) and control littermates. Ovarian follicle development, ovulation, and litter sizes were also equivalent between genotypes. Testis weights and sperm counts did not differ between cKO and control males. Following gonadectomy, increases in LH secretion were enhanced in cKO animals. Though FSH levels did not differ between genotypes, post-gonadectomy increases in pituitary Fshb and gonadotropin α subunit expression were more pronounced in cKO mice. These data indicate that ATF3 can selectively stimulate Fshb transcription in vitro but is not required for FSH production in vivo.
2023-06-28 | GSE220809 | GEO
Project description:DRD2 agonists are effective in treating pituitary tumors. To fathom the β-arresin-dependent mechanisms underlying DRD2-mediated pituitary tumor growth suppression,we applied RNA-seq analysis to rat pituitary MMQ cells treated with a DRD2 β-arresin-biased agoinst, UNC9994.MMQ cells were treated with UNC9994(15μM) or vehecle control for 12 h or 24 h and then subject to RNA-seq analysis.We found oxidative-stress-related genes such as Nqo1 and Hmox1 were upregulated by UNC9994, revealing oxidative stress may be the basis of UNC9994-induced tumor growth suppression. Our study represents the first detailed analysis of transcriptomes in rat pituitary MMQ cells treated with DRD2 β-arresin-biased agonist.The significance of altered expression of specific transcripts will enhance our understanding of DRD2 signaling in pituitary tumor cells.
2023-07-13 | GSE154351 | GEO