Candidate Genes for Panhypopituitarism identified by gene expression profile
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE30863 | GEO | 2011/12/14
SECONDARY ACCESSION(S): PRJNA146153
REPOSITORIES: GEO
Similar Datasets
Project description:Prop1 controls the expression of genes besides Pit1 that are important for cell mgration, survival and differentiation in the mouse and human pituitary gland. Microarray analysis was used to compare pituitary RNA from newborn Prop1 and Pit1 mutants and their wild type littermates. Total RNA was collected and pooled from Prop1df/df, Porp1+/+, Pit1dw/dw, and Pit+/+ at the age of P1. 5 pools per genotype were hybridized to the Affymetrix Mouse Genome 430 2.0 array.
2011-12-14 | E-GEOD-30863 | biostudies-arrayexpress
Project description:Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the regulation of pituitary transcription factors Hesx1 and Pit1. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant tissues, isolated stem cells and engineered cell lines. We determined that PROP1 is essential for maintaining proliferation of stem cells and stimulating them to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to and represses claudin 23, characteristic of epithelial cells, and it activates EMT inducer genes: Zeb2, Notch2 and Gli2. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.
2016-07-11 | GSE77302 | GEO
Project description:Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the regulation of pituitary transcription factors Hesx1 and Pit1. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant tissues, isolated stem cells and engineered cell lines. We determined that PROP1 is essential for maintaining proliferation of stem cells and stimulating them to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to and represses claudin 23, characteristic of epithelial cells, and it activates EMT inducer genes: Zeb2, Notch2 and Gli2. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.
2016-07-11 | GSE77357 | GEO
Project description:Dietary vitamin A is metabolized into bioactive retinoic acid in vivo and regulates the development of many embryonic tissues. Retinoic acid signaling is active in the oral ectoderm-derived tissues of the neuroendocrine system, but its role there has not yet been fully explored. We show here that retinoic acid signaling is active during pituitary organogenesis and dependent on the pituitary transcription factor Prop1. Prop1-mutant mice show reduced expression of the aldehyde dehydrogenase gene Aldh1a2, which metabolizes the vitamin A-intermediate retinaldehyde into retinoic acid. In order to elucidate the specific function of RA signaling during neuroendocrine development, we studied a conditional deletion of Aldh1a2 and a dominant-negative mouse model of inhibited retinoic acid signaling during pituitary organogenesis. These models partially phenocopy Prop1-mutant mice by exhibiting embryonic pituitary dysmorphology and reduced hormone expression, especially of thyroid-stimulating hormone. These findings establish the critical role of retinoic acid in embryonic pituitary stem cell progression to differentiated hormone cells and raise the question of gene-by-environment interactions as contributors to pituitary development and disease.
2020-02-26 | GSE142074 | GEO
Project description:Pituitary neuroendocrine tumors (PitNET)/adenomas are classified according to cell lineage, which requires immunohistochemistry for the transcription factors (TFs) PIT1, SF1, and TPIT. Co-expression of PIT1/SF1 was previously reported in PitNETs, which otherwise correspond to the somatotroph lineage. However, little is known about the clinicopathological features of these tumors. We compiled an in-house case series of 100 tumors, previously diagnosed as densely or sparsely granulated somatotroph PitNETs. Following TF staining, histopathological features associated with PIT1/SF1-coexpression were assessed. Global DNA methylation profiling was conducted on 31 of 100 in-house samples and integrated with publicly available sample data. The majority (74%, 52/70) of our densely granulated somatotroph PitNETs (DGST) unequivocally co-expressed PIT1 and SF1 (DGST-PIT1/SF1). None of our SGST (0%, 0/30) stained positive for SF1 (SGST-PIT1). Integrated molecular analyses including publicly available sample data confirmed that DGST-PIT1/SF1, DGST-PIT1 and SGST-PIT1 represent distinct tumour subtypes. In summary, we spotlight that a substantial proportion of previously diagnosed densely granulated somatotroph PitNET co-express PIT1 and SF1 and exhibit clinical, histopathological, and molecular distinctness from other pure PIT1-lineage somatotroph PitNET.
2024-01-24 | GSE246645 | GEO
Project description:Transcription factors and signaling pathways that regulate stem cells and specialized hormone-producing cells in the pituitary gland have been the subject of intense study and have yielded a mechanistic understanding of pituitary organogenesis and disease. Yet, the regulation of stem cell proliferation and differentiation, the heterogeneity among specialized hormone-producing cells, and the role of non-endocrine cells in the gland remain important, unanswered questions. Recent advances in single-cell RNA sequencing (scRNAseq) technologies provide new avenues to address these questions. We performed scRNAseq on approximately 13,663 cells pooled from six whole pituitary glands of 7-week-old C57BL/6 male mice. We identified pituitary endocrine and stem cells in silico, as well as other support cell-types such as endothelia, connective tissue, and red and white blood cells. Differential gene expression analyses identify known and novel markers of pituitary endocrine and stem cell populations. We demonstrate the value of scRNAseq by in vivo validation of a novel gonadotrope-enriched marker, Foxp2. We present novel scRNAseq data of in vivo pituitary tissue, including data from agnostic clustering algorithms which suggest the presence of a somatotrope subpopulation enriched in sterol/cholesterol synthesis genes. At the same time, we show that incomplete transcriptome annotation can cause false negatives on some scRNAseq platforms that only generate 3’ transcript end sequences, and use in vivo data to recover reads of the pituitary transcription factor Prop1. Ultimately, scRNAseq technologies represent a significant opportunity to address longstanding questions regarding the development and function of the different populations of the pituitary gland throughout life.
2018-10-19 | GSE120410 | GEO
Project description:Ustilago maydis is a basidiomycete fungus that causes smut disease in maize. Most prominent symptoms of the disease are plant tumors, which can be induced by U. maydis on all aerial parts of the plant. We identified two linked genes, pit1 and pit2, which are specifically expressed during plant colonization. Deletion mutants for either pit1 or pit2 are unable to induce tumor development and elicit plant defense responses. We used the Affymetrix maize genome array to analyze the transcriptional responses of maize to deletion pit1 and pit2 mutants and found plant responses to both mutants being not significantly distinguishable.
2011-07-01 | GSE28479 | GEO
Project description:The purpose of this research is to determine whether the drug, Bevacizumab (a monoclonal anti VEGF-A antibody), which is approved to treat patients with metastatic colon cancer induces hyperprolactinemia (increased prolactin secretion) in humans with intact pituitary function. Past studies have shown Bevacizumab to shrink tumor size and also increase prolactin levels. The mechanism of the hyperprolactinemia might be inhibition of pituitary portal vein transport, suggesting that Bevacizumab induces prolactin secretion from normal lactotrophs in the pituitary gland.
Patients who have been treated with Bevacizumab for at least one month will be recruited to participate.
The subjects who are being treated with Bevacizumab by Dr. Stephen Wolin (a sub-investigator) will be screened by him for study eligibility. Dr. Wolin will approach eligible patients with all the information and background of the study and see if they have an interest in being consented.
If consented, there will be 2 blood draws for the research that is not part of their standard care in which 10 ml of blood is collected and prolactin, growth hormone, IGF-I, TSH, thyroxine, ACTH, and cortisol will be measured. One 5ml blood draw will occur before the administration of Bevacizumab and the second 5 ml blood draw will occur after the administration of the Bevacizumab. The investigators will then review the laboratory results. The blood tests are of the hormones of the pituitary gland to test pituitary function and see if there are any abnormalities with the secretions of the gland. Pituitary function abnormalities and hyperprolactinemia are diagnosed by looking at hormone levels in the blood and comparing them to the normal reference ranges.
This study will only involve 10 subjects and will be conducted entirely at Cedars-Sinai Medical Center.
| 2077752 | ecrin-mdr-crc
Project description:The regulation of pituitary function via the hypothalamus and via intra-pituitary connections represents a complex system. Though hormones secreted from the pituitary glands have been well studied, overall information of proteins expressed in the pituitary glands is very limited. Protein expression profiling of normal pituitary tissue may lead to discovery of novel proteins playing an important role in the physiology of pituitary glands and can lead to better understanding of pituitary gland diseases. We aimed to carry out systematic proteomic profiling of adenohypophysis from human pituitary glands using high-resolution Fourier transform mass spectrometer. A total of 2,175 proteins were identified in this study of which, 105 proteins were identified for the first time as compared to high throughput proteomic-based studies from human pituitary glands. The comprehensive list of proteins identified in this study will facilitate the better understanding the role of this important gland in health and disease.
2019-01-02 | PXD005819 | Pride
Project description:Ustilago maydis is a basidiomycete fungus that causes smut disease in maize. Most prominent symptoms of the disease are plant tumors, which can be induced by U. maydis on all aerial parts of the plant. We identified two linked genes, pit1 and pit2, which are specifically expressed during plant colonization. Deletion mutants for either pit1 or pit2 are unable to induce tumor development and elicit plant defense responses. We used the Affymetrix maize genome array to analyze the transcriptional responses of maize to deletion pit1 and pit2 mutants and found plant responses to both mutants being not significantly distinguishable. U. maydis infected parts of maize seedling leaves were dissected 4 days after inoculation with strain SG200Dpit1 and SG200Dpit2, respectively. We previously submitted data of maize leaves that were treated with the progenitor wild type strain SG200 as well as mock-infections under identical experimetal conditions (GEO: GSE10023, 4d mock and 4d SG200 Samples, equivalent record in Arrayexpress: E-GEOD-10023). These data served as controls for this experiment.
2011-07-01 | E-GEOD-28479 | biostudies-arrayexpress