OBJECTIVE: Acromegaly is a rare endocrine disorder with excess growth hormone (GH) production. This disorder has important metabolic effects in insulin resistance and lipolysis. The objective of this study was to explore transcriptional changes induced by GH in adipose tissue. METHODS: The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex-vivo for lipolysis and ceramide levels. Adipose tissue was analyzed by RNA sequencing (RNA-seq). RESULTS: There was evidence of reduced insulin sensitivity based on the increase in fasting glucose, insulin and HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3) as well as several novel transcriptional changes, some of which may be important for GH signal regulation (PTPN3 and PTPN4) and the effect of GH on growth and proliferation. Several transcripts could potentially be important in GH-induced metabolic changes. Specifically, induction of LPL, ABHD5, and ACVR1C could contribute to enhanced lipolysis and may explain the suggestive enhancement of adipose tissue lipolysis in acromegaly patients as reflected by glycerol release from the explants of the two groups of patients (p=0.09). Higher expression of SCD and TCF7L2 could contribute to insulin resistance. Expression of HSD11B1 was reduced and GR was increased, predicting modified glucocorticoid activity in acromegaly. CONCLUSIONS: We identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. Overall design: DESIGN: Patients with acromegaly (n=9) or non-functioning pituitary adenoma (n=11) were prospectively observed from March 2011 to June 2012. Sequencing was performed on RNA from 7 acromegaly patients and 11 controls.
Gene Expression Signature in Adipose Tissue of Acromegaly Patients.
No sample metadata fields
View SamplesGlucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNA sequencing on subcutaneous adipose tissue from patients with Cushing's disease (n=5) compared to patients with non-functioning pituitary adenomas (n=11). We found higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in a model system, we subjected mice to dexamethasone treatment for 12 weeks and analyzed their inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the co-morbidities associated with chronic elevations of glucocorticoids Overall design: DESIGN: Patients with cushing's (n=5) or non-functioning pituitary adenoma (n=11) were prospectively observed from March 2011 to June 2012.
Gene expression changes in subcutaneous adipose tissue due to Cushing's disease.
No sample metadata fields
View SamplesWe performed RNA sequencing analysis of hepatic gene expression a few hours after amlexanox treatment, and identified over 1700 differentially expressed genes. Pathway analysis of these differentially regulated genes revealed that the top two most enriched pathways were the adipocytokine signaling pathway and the Jak-STAT signaling pathway. Overall design: RNA-seq analysis of hepatic gene expression was used to identify differentially expressed genes in response to Amlexanox treatment.
A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis.
No sample metadata fields
View SamplesAfter inactivation of Hoxa5 at postnatal days (P)1-P4, we established RNA-seq profiling with RNA extracted from P21 brainstem of tamoxifen-treated Hoxa5flox/flox;CMV-CreERT2+/- (Hoxa5 cKO) pups and tamoxifen-treated Hoxa5flox/flox;CMV-CreERT2-/-(Hoxa5 control) pups Overall design: To explore HOXA5 downstream target genes in the postnatal brainstem, we carried out transcriptomic analyses by RNA-Seq using a model of postnatal Hoxa5 loss-of-function. We induced Hoxa5 inactivation after birth (P1 to P4) using the tamoxifen-inducible CMV-CreERT2 mice and conditional Hoxa5 floxed allele mice (Hoxa5flox). RNA was extracted from the brainstem of P21 tamoxifen-treated Hoxa5flox/flox;CMV-CreERT2+/- pups and from tamoxifen-treated Hoxa5flox/flox;CMV-CreERT2-/- littermates (see extract protocol).
Conditional Loss of <i>Hoxa5</i> Function Early after Birth Impacts on Expression of Genes with Synaptic Function.
Specimen part, Treatment, Subject
View SamplesThis experiment was a time course performed over 24 hours to look at the effects on gene expression of exposure to low red:far-red ratio light in Arabidopsis thaliana plants. In this way genes involved in the shade avoidance response might be identified. This experiment was designed for gene identification only and containes no replicates,genes identified were verified by quantitative PCR for publication.
Gating of the rapid shade-avoidance response by the circadian clock in plants.
Specimen part, Disease, Disease stage, Subject
View SamplesAbstract: Alternative splicing (AS) plays a major role in the generation of proteomic diversity and in gene regulation. However, the role of the basal splicing machinery in regulating AS remains poorly understood. Here we show that the core snRNP protein SmB/B’ self-regulates its expression by promoting the inclusion of a highly-conserved alternative exon in its own pre-mRNA that targets the spliced transcript for nonsense-mediated mRNA decay (NMD). Depletion of SmB/B’ in human cells results in reduced levels of snRNPs and in a striking reduction in the inclusion levels of hundreds of alternative exons, with comparatively few effects on constitutive exon splicing levels. The affected alternative exons are enriched in genes encoding RNA processing and other RNA binding factors, and a subset of these exons also regulate gene expression by activating NMD. Our results thus demonstrate a role for the core spliceosomal machinery in controlling an exon network that appears to modulate the levels of many RNA processing factors. Overall design: HeLa cells were transfected with a control non-targeting siRNA pool (siNT), or with siRNA pools designed to knockdown SmB/B'' or SRSF1 (also known as SF2/ASF/SFRS1). Sequence reads were aligned to exon-exon junction sequences in a database of EST/cDNA-mined cassette-type alternative splicing events. Processed data files (.bed and .txt) provided as supplementary files on the Series record. Processed data file build information: hg18.
Regulation of alternative splicing by the core spliceosomal machinery.
No sample metadata fields
View SamplesTumors that show evidence of epithelial to mesenchymal transition (EMT) have been associated with metastasis, drug resistance, and poor prognosis. EMT may alter the molecular requirements for growth and survival in different contexts, but the underlying mechanisms remain incomplete. Given the heterogeneity along the EMT spectrum between and within tumors it is important to define the requirements for growth and survival in cells with an epithelial or mesenchymal phenotype to maximize therapeutic efficacy.
Epithelial-to-mesenchymal transition rewires the molecular path to PI3K-dependent proliferation.
Specimen part, Cell line, Treatment
View SamplesThe adoptive transfer of chimeric antigen receptor- (CAR) modified T cells is revolutionizing the treatment of B cell malignancies and has the potential to be applied to other diseases. CARs redirect T cell specificity by linking an antigen recognition domain to T cell signaling modules comprised of CD3z to provide signal 1, and CD28 or 4-1BB to provide costimulation. CD28/CD3z and 4-1BB/CD3z CARs confer differences in effector function and cell fate that affect clinical efficacy and toxicity. These differences may result from activation of divergent transcriptional programs. To gain this insight, we analyzed changes in gene expression in stimulated and resting CD28/CD3z or 4-1BB/CD3z CAR T cells. CD28/CD3z CAR stimulation initiated more marked early transcriptional changes with greater fold increases in the expression of effector molecules including GZMB, IFNG, IL2, TNF, and IL6. Direct comparison of CD28/CD3z and 4-1BB/CD3z samples stimulated for 6 hours identified 1,673 differentially expressed genes. Of these, the memory T cell-associated genes KLF2, IL7R, and FAM65B were expressed at lower levels in CD28/CD3z CAR T cells. KLF2 and IL7R are FOXO transcription factor family targets and we found that FOXO4 expression was similarly reduced in CD28/CD3z CAR T cells. CD28/CD3z CAR stimulation induces an effector T cell-like transcriptional profile that may underlie the decreased persistence and increased risks of toxicities observed with CD28/CD3z CAR T cells in early clinical trials. Overall design: Purified CD28/CD3z and 4-1BB/CD3z CAR T cells were prepared from healthy donors and stimulated by incubation with anti-CAR beads, or left unstimulated by incubation with control beads. Total RNA was harvested 6 or 24 hours after treatment. Three biological replicates for each treatment condition were prepared, yielding 24 total samples for analysis. A42 and A44 denote 4-1BB/CD3z CARs, A43 and A45 denote CD28/CD3z CARs.
Phosphoproteomic analysis of chimeric antigen receptor signaling reveals kinetic and quantitative differences that affect cell function.
Subject, Time
View Samplesaffy_seed_kinetic_wheat - affy_seed_kinetic_wheat - Study gene expression during the grain developmental -The aim of the study is to identify the genes that are differentially expressed during the grain development in wheat.-Study gene expression during the grain developmental Sample at 100 degree days, year 2004 and 2006 Sample at 200 degree days, year 2004 and 2006 Sample at 250 degree days, year 2004 and 2006 Sample at 300 degree days, year 2004 and 2006 Sample at 400 degree days, year 2004 and 2006
RNA-seq in grain unveils fate of neo- and paleopolyploidization events in bread wheat (Triticum aestivum L.).
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The bHLH transcription factor POPEYE regulates response to iron deficiency in Arabidopsis roots.
Age, Specimen part
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