The source of aldosterone in 30 to 40 % of patients with primary hyperaldosteronism (PA) is unilateral aldosterone-producing adenoma (APA). The mechanisms causing elevated aldosterone production in APA are unknown. Herein, we examined expression of G-protein coupled receptors (GPCR) in APA and demonstrate that compared to normal adrenals there is a general elevation of certain GPCR in many APA and/or ectopic expression of GPCR in others. RNA samples from normal adrenals (n = 5), APAs (n = 10), and cortisol-producing adenomas (CPAs) (n=13) were used on 15 genomic expression arrays, each of which included 223 GPCR transcripts presented in at least one out of 15 of the independent microarrays. The array results were confirmed using real-time RT-PCR (qPCR). Four GPCR transcripts exhibited a statistically significant increase that was greater than 3-fold compared to normal adrenals, suggesting a general increase in expression compared to normal adrenal glands. Four GPCR transcripts exhibited a greater than 15-fold increase of expression in one or more of the APA samples compared to normal adrenals. qPCR analysis confirmed array data and found the receptors with the highest fold increase in APA expression to be luteinizing hormone receptor (LH-R), serotonin receptor 4 (HTR4), gonadotropin-releasing hormone receptor (GnRHR), glutamate receptor metabotropic 3 (GRM3), endothelin receptor type B-like protein (GPR37), and ACTH receptor (MC2R). There are also sporadic increased expressions of these genes in the CPAs. Together, these findings suggest a potential role of altered GPCR expression in many cases of PA and provide candidate GPCR for further study.
G-protein-coupled receptors in aldosterone-producing adenomas: a potential cause of hyperaldosteronism.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrator regulates transcriptional initiation and pause release following activation.
Disease, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Anti-diabetic rosiglitazone remodels the adipocyte transcriptome by redistributing transcription to PPARγ-driven enhancers.
Cell line, Treatment, Time
View SamplesRosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for PPARg, the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to the NR on DNA, explains positive regulation of gene expression, but ligand-dependent repression is not well understood. We have now addressed this issue by studying the direct effects of rosiglitazone on gene transcription, using global run-on sequencing (GRO-seq). Rosi-induced changes in gene body transcription were pronounced after 10 minutes and correlated with steady-state mRNA levels as well as with transcription at nearby enhancers (eRNAs). Upregulated eRNAs occurred almost exclusively at PPARg binding sites, to which rosi treatment recruited the coactivator MED1. By contrast, transcriptional repression by rosi involved a loss of MED1 from eRNA sites devoid of PPARg and enriched for other TFs including AP-1 factors and C/EBPs. Thus, rosi activates and represses transcription by fundamentally different mechanisms that could inform the future development of antidiabetic drugs.
Anti-diabetic rosiglitazone remodels the adipocyte transcriptome by redistributing transcription to PPARγ-driven enhancers.
Cell line, Treatment, Time
View SamplesWe investigated the genomic occupancy of INTS11, in normal condition and after stimulation of EGF. Total RNAPII was profiled in the presence or absence of INTS11, along with the Super Elongation Complex proteins AFF4 and ELL2. Additionally, we extensively examined the transcriptional response to EGF, before and after depletion of INTS11, using RNA-seq on ribosome-depleted total RNA and Global Run-on sequencing (GRO-seq).
Integrator regulates transcriptional initiation and pause release following activation.
Cell line, Treatment
View SamplesThe disrupted genetic mechanisms underlying neural abnormalities in Autism Spectrum Disorder remain mostly unknown and speculative. No biological marker nor genetic signature is currently available to assist with early diagnosis.
Prediction of autism by translation and immune/inflammation coexpressed genes in toddlers from pediatric community practices.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Specimen part, Treatment
View SamplesWe used microarrays to detail the global gene transcription underlying T cells activation during the first 24 hours after stimulation.
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Specimen part, Treatment
View SamplesWe used microarrays to detail the global gene transcription effect of Dec1 underlying T cells activation during the first 24 hours after stimulation.
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Specimen part, Treatment
View SamplesPeripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMfs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMfs to populate the niche and that the presence of beMfs does not alter behavior. Furthermore, beMfs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMfs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMfs may be possible with irradiation-free conditioning regimens. Overall design: Microglia were isolated from the brains of adult male c57BL/6 mice given bone marrow tranplants (BMT) with or without head shield. All mice received PLX5622 for 2 weeks, then placed and normal chow to recoever. Some mice were then challenged with LPS. Cells were isolated by MACS using CD11b magnetic beads.
Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.
Age, Specimen part, Cell line, Treatment, Subject
View Samples