Estrogen-related receptor (ERR) alpha is an orphan nuclear receptor highly expressed in the kidneys. ERRalpha is implicated in renal sodium and potassium homeostasis and blood pressure regulation. We used microarray analysis to identify differentially expressed genes in ERR alpha knockout mice kidneys versus wild-type. The results provide insight on the roles of ERRalpha in the kidney.
Physiological genomics identifies estrogen-related receptor alpha as a regulator of renal sodium and potassium homeostasis and the renin-angiotensin pathway.
Sex, Specimen part
View SamplesPurpose: we tested the hypothesis that Hltf deletion in placenta either caused or exacerbated neonatal hypoglycemia via Hif-1a regulation of nutrient transporters. Methods: Individual samples [1 term placenta/sample x 5 biological replicates for test and control littermate female mice = 10 total samples] were flash frozen and sent to Otogenetics Corp. (Norcross, GA) for RNA-seq assays. Paired-end 100 nucleotide reads were aligned to genomic assembly mm10 and analyzed using the platform provided by DNAnexus, Inc. (Mountain View, CA). Results: There was no measureable evidence of uteroplacental dysfunction or fetal compromise. Conclusion: Our study is the first to show only the truncated Hltf isoform is expressed in E18.5 term placenta, and we identified a functional link between alternative splicing of Hltf and immunosuppression at the feto-maternal interface. Overall design: Placental mRNA profiles of E18.5 term placenta from five wild type control and five Hltf null mouse samples were generated by deep sequencing by Illumina HiSeq2000/2500.
Alternative splicing of helicase-like transcription factor (Hltf): Intron retention-dependent activation of immune tolerance at the feto-maternal interface.
Specimen part, Cell line, Subject
View SamplesTotal RNA was isolated from 3 WT and 3 ERRa null hearts and independent hybridizations were performed using MOE430 2.0 microarrays. Expression profiling was conducted to determine changes in gene expression in hearts lacking ERRa. The expression of genes involved in heart and muscle development, muscle contraction, lipid metabolism, OxPhos, protein metabolism and transcription were affected by the loss of ERRa.
Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma.
Sex, Specimen part
View Samples3 ventricles from E18.5 male mice were pooled for each array. Three arrays per genotype.
ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart.
No sample metadata fields
View SamplesIn chronic lymphocytic leukemia (CLL), 13q14 and 11q22-23 deletions are found in 2/3 of the cases. 11q22-23 deletions are associated with poor survival, whereas 13q14 deletions as single abnormality are often found in indolent disease forms. The molecular basis for this difference in prognosis is not known.
Expression analysis of genes located in the minimally deleted regions of 13q14 and 11q22-23 in chronic lymphocytic leukemia-unexpected expression pattern of the RHO GTPase activator ARHGAP20.
Specimen part, Disease, Disease stage
View SamplesPurpose: CEBPA mutations are found as either biallelic (biCEBPA) or monoallelic (moCEBPA). We set out to explore whether the kind of CEBPA mutation is of prognostic relevance in cytogenetically normal AML (CN-AML).
Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome.
Specimen part
View SamplesPediatric medulloblastoma is considered a highly heterogeneous disease, and a new strategy of risk stratification to optimize therapeutic outcomes is required. We aimed to investigate a new risk-stratification approach based on expression profiles of medulloblastoma cohorts. We analyzed gene expression profiles of 30 primary medulloblastomas and detected strong evidence that poor survival outcome was significantly associated with mRNA expression profiles of 17p loss. However, it was not supported in independent cohorts from previously published data (n=100). We speculated that this controversy might come from complex conditions of two important prognostic determinants, loss of tumor suppressors (chromosome 17p) and high expression of oncogenes, c-myc (MYC) or N-myc (MYCN). Simultaneous consideration of these two factors led to a new subgrouping of patients, exhibiting obviously different survival expectancies between the subgroups. Patients with up-regulated WNT signalings were always pre-defined as an independent subgroup, which ultimately removed confounding effect arising from contradictory outcome, favorable prognosis of WNT medulloblastomas despite their high MYC/MYCN expression level. We also found that age is a significant prognostic marker after adjusting for 17p and MYC/MYCN status. Diminished survival in age <3 years was more substantial in groups with high expression of MYC/MYCN or 17p loss, indicating survival outcome might be coordinately affected by these three factors. We suggest a more tailored and easily applicable subgrouping system based on expression profiles of chromosome 17p and MYC/MYCN, while separating WNT medulloblastoma as an independent subgroup, which could provide the basis for a novel risk-stratification strategy in pediatric medulloblastoma.
Prognostic classification of pediatric medulloblastoma based on chromosome 17p loss, expression of MYCC and MYCN, and Wnt pathway activation.
Sex, Specimen part
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Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer.
Cell line, Treatment
View SamplesWhether the nuclear fraction of mTOR plays a role in prostate cancer (PCa) and can participate in direct transcriptional crosstalk with the androgen receptor (AR) is as yet unknown. The intersection of gene expression, DNA binding-events, and metabolic studies uncovered the existence of a nuclear mTOR-AR transcriptional axis dictating the metabolic rewiring and nutrient usage of PCa cells. In human clinical specimens, nuclear localization of mTOR was significantly associated with metastasis and castration-resistant PCa (CRPC), correlating with a sustained metabolic gene program governed by mTOR in that context. This study thus uncovers an unexpected function of mTOR and underscores a paradigm shift from AR to mTOR as being the master transcriptional regulator of cell metabolism during PCa progression.
Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An FGFR3/MYC positive feedback loop provides new opportunities for targeted therapies in bladder cancers.
Cell line
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