Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rathke’s Cleft-Like Cysts Arise From Isl1 Deletion in Murine Pituitary Progenitors

ABSTRACT: The transcription factor ISL1 is expressed in pituitary gland stem cells and the thyrotrope and gonadotrope lineages. Pituitary-specific Isl1 deletion causes hypopituitarism with increased stem cell apoptosis, reduced differentiation of thyrotropes and gonadotropes, and reduced body size. Conditional Isl1 deletion causes development of multiple Rathke’s cleft-like cysts, with 100% penetrance. Foxa1 and Foxj1 are abnormally expressed in the pituitary gland and associated with a ciliogenic gene expression program in the cysts. We confirmed expression of FOXA1, FOXJ1 and stem cell markers in human Rathke's cleft cyst tissue, but not craniopharyngiomas, which suggests these transcription factors are useful, pathological markers for diagnosis of Rathke's cleft cysts. These studies support a model whereby expression of ISL1 in pituitary progenitors drives differentiation into thyrotropes and gonadotropes, and without it, activation of FOXA1 and FOXJ1 permits development of an oral epithelial cell fate with mucinous cysts. This pituitary-specific Isl1 mouse knockout sheds light on the etiology of Rathke's cleft cysts and the role of ISL1 in normal pituitary development.

ORGANISM(S): Mus musculus

PROVIDER: GSE149019 | GEO | 2020/04/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Rathke’s Cleft-Like Cysts Arise From Isl1 Deletion in Murine Pituitary Progenitors

Project description:Rathke’s Cleft-Like Cysts Arise From Isl1 Deletion in Murine Pituitary Progenitors

| PRJNA627154 | ENA

Transcriptomic changes in the pituitary when pituitary enhancer of the Nr5a1 gene is deleted

Project description:NR5A1 is expressed in the pituitary gonadotropes and regulates their functional differentiation. We have previously identified a pituitary-specific enhancer region located in the 6th intron of the Nr5a1 gene. In this study, deletion of the pituitary enhancer by genome editing abolished the expression of NR5A1 in the pituitary gland, confirming the functional importance of the enhancer. Transcriptomic changes in the enhancer-deleted mouse pituitary were revealed in both males and females.

2022-10-28 | GSE216468 | GEO

Transcriptome of the NR5A1 expressing pituitary gonadotropes

Project description:NR5A1 is expressed in the pituitary gonadotropes and regulates their functional differentiation. In this study, transcriptomes of the pituitary gonadotropes which are sorted from Ad4BP-BAC-EGFP mice were revealed in males and females.

2022-10-28 | GSE216466 | GEO

Epigenome-wide association study of the whole blood DNA in men with congenital hypopituitarism disease

Project description:Congenital hypopituitarism (CH) is chracterized with one or more hormones secreted deficiency by the pituitary gland, which leads to metabolic disorders, amenorrhea and infertility of the patients; however, the involved molecular mechanisms has not yet fully elucidated. We examined genome-wide methylation levels of whole blood DNA in 12 CH patients and 12 age-matched controls using Illumina HumanMethylation450 array. Significantly different methylated loci were further validated in another 40 patients and 40 controls with quantitative bisulfite pyrosequencing method.

2017-12-06 | GSE107737 | GEO

Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism

Project description:Inter-organ communication is a major hallmark of health and is often orchestrated by hormones released by the anterior pituitary gland. Pituitary gonadotropes secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to regulate gonadal function and control fertility. Whether FSH and LH also act on organs other than the gonads is debated. Here, we found that gonadotrope depletion in adult female mice triggers profound hypogonadism, obesity, glucose intolerance, fatty liver, and bone loss. The absence of sex steroids precipitates these phenotypes, with the notable exception of fatty liver, which results from ovary-independent actions of FSH. We uncover paracrine FSH action on pituitary corticotropes as a novel mechanism to restrain the production of corticosterone and prevent hepatic steatosis. Our data demonstrate that functional communication of two distinct hormone-secreting cell populations in the pituitary regulates hepatic lipid metabolism.

2023-01-11 | GSE216096 | GEO

Transcriptome and methylome analysis reveal three cellular origins of pituitary tumors

Project description:The pituitary tumors (PA) arise in adenohypophyseal cells and are the second most common tumor in central nervous system. Reflective of their monoclonal cell of origin these tumors could be classified according to the hormone that they produce. The mutational and copy number variation burden in these tumors are scarce, indicating other molecular events are involved in pituitary tumorigenesis. Here we show throughout transcriptome and methylome analysis that there are three readily distinctive molecular signatures. The first group is comprised by the gonadotropes, null cell and silent corticotroph PA, the second group comprised by ACTH PA and the group cluster together the TSH-, PRL- and GH- PA. These groups showed CACNA2D4, EPHA4 and SLIT1 gene up-regulation, respectively. Pathway enrichment analysis support the previous observations. The calcium signaling pathway is characteristic for gonadotropes null cell and silent corticotroph, the Renin-Angiotensin system for the ACTH PA and the Fatty acid metabolisms for the TSH-, PRL-, GH- cluster. The analysis of scRNA-seq from non-tumoral pituitary tissue revealed that these three groups originate since the pituitary development/embryogenesis. The immune cell infiltration landscape revealed that PA could be potentially infiltrated by NK and mast cells. Taken together these results correlate with the expression of the NR5A1, TBX19 and POU1F1 transcription factors, which drive pituitary embryogenesis and theoretically tumorigenesis and potentially indicates three divergent cell precursors cells. We used microarrays to detail the molecular alteration in PA compared to non-tumoral gland.

2020-11-16 | GSE147786 | GEO

PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells [RNA-Seq]

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

PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells [ChIP-Seq]

2016-07-11 | GSE77302 | GEO

Optimized amplification and single-cell analysis identify GnRH-mediated activation of Rap1b in primary rat gonadotropes.

Project description:Identifying the early gene program induced by GnRH would help understand how GnRH-activated signaling pathways modulate gonadotrope secretory response. We previously analyzed GnRH-induced early genes in LbT2 cells, however these lack GnRH self-potentiation, a physiological attribute of gonadotropes. To minimize cellular heterogeneity, rat primary pituitary cultures were enriched for gonadotropes by 40-60% using a sedimentation gradient. Given the limited number of gonadotropes, RNA was amplified prior to microarray analysis. Thirty-three genes were up-regulated 40 minutes after GnRH stimulation. Real-time PCR confirmed regulation of several transcripts including fosB, c-fos, egr-2 and rap1b, a small GTPase and member of the Ras family. GnRH stimulated rap1b gene expression in gonadotropes, measured by a sensitive single cell assay. Immunocytochemistry revealed increased Rap1 protein in GnRH-stimulated gonadotropes. These data establish rap1b as a novel gene rapidly induced by GnRH and a candidate to modulate gonadotropin secretion in rat gonadotropes. Primary rat gonadotrope cells were exposed to 10 nM GnRH for 40 min, then harvested and processed for RNA extraction using a Qiagen RNeasy mini kit (Qiagen, Valencia, CA). A total of 12 Affymetrix Rat Expression Array 230 v2.0, namely 6 GnRH-treated and 6 vehicle-treated samples, each containing 31,000 gene clusters, were used. Data analysis was performed by Affymetrix GeneChip Operating System (GCOS). A gene was considered to be up-regulated by GnRH if there is at least 50% concordance across multiple pairwise comparisons of GnRH- vs. vehicle-treated microarrays, and if the fold-change was at least 1.50.

2011-08-16 | E-GEOD-31399 | biostudies-arrayexpress

FSH-deficiency in gonadotrope-specific GATA2 knockout mice is associated with a loss of gremlin expression [snATAC-Seq]

Project description:Mammalian reproduction is dependent on the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, which are secreted by pituitary gonadotrope cells. The zinc-finger transcription factor, GATA2, was previously implicated in FSH production in male mice, although its mechanisms of action and role in females were not determined. To address these gaps in knowledge, we generated and analyzed gonadotrope-specific Gata2 knockout mice using the Cre-lox system. While conditional knockout (cKO) males exhibited ~50% reductions in serum FSH levels and pituitary FSHβ subunit (Fshb) expression relative to controls, FSH production was apparently normal in cKO females. RNA-seq analysis of purified gonadotropes from control and cKO males revealed a profound decrease in expression of gremlin (Grem1), a bone morphogenetic protein (BMP) antagonist. Grem1 was expressed in gonadotropes, but not other cell lineages, in the adult male mouse pituitary. Gata2, Grem1, and Fshb mRNA levels were significantly higher in pituitaries of wild-type males relative to females but decreased in males treated with estradiol and increased following ovariectomy in control but not cKO females. Recombinant gremlin stimulated Fshb expression in pituitary cultures from wild-type mice. Collectively, the data suggest that GATA2 promotes Grem1 expression in gonadotropes and that the gremlin protein potentiates FSH production. The mechanisms of gremlin action have not yet been established but may involve attenuation of BMP binding to activin type II receptors in gonadotropes, potentiating induction of Fshb transcription by activins or related ligands.

2022-07-14 | GSE190064 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data