Schizophrenia (SCZ) and bipolar disorder (BPD) are polygenic disorders with many genes contributing to their etiologies. The aim of this investigation was to search for dysregulated molecular and cellular pathways for these disorders as well as psychosis. We conducted a blood-based microarray investigation in two independent samples with SCZ and BPD from San Diego (SCZ=13, BPD=9, control=8) and Taiwan [data not included](SCZ=11, BPD=14, control=16). Diagnostic groups were compared to controls, and subjects with a history of psychosis [PSYCH(+): San Diego (n=6), Taiwan (n=14)] were compared to subjects without such history [PSYCH(-): San Diego (n=11), Taiwan (n=14)]. Analyses of covariance comparing mean expression levels on a gene-by-gene basis were conducted to generate the top 100 significantly dysregulated gene lists for both samples by each diagnostic group. Gene lists were imported into Ingenuity Pathway Analysis (IPA) software. Results showed the ubiquitin proteasome pathway (UPS) was listed in the top ten canonical pathways for BPD and psychosis diagnostic groups across both samples with a considerably low likelihood of a chance occurrence (p = .001). No overlap in dysregulated genes populating these pathways was observed between the two independent samples. Findings provide preliminary evidence of UPS dysregulation in BPD and psychosis as well as support further investigation of the UPS and other molecular and cellular pathways for potential biomarkers for SCZ, BPD, and/or psychosis.
Preliminary evidence of ubiquitin proteasome system dysregulation in schizophrenia and bipolar disorder: convergent pathway analysis findings from two independent samples.
Sex, Age, Disease
View SamplesWe report the application of RNA-Seq analysis to determine the transcriptional responses to Mn dose, ranging from physiological to toxicological levels in human SH-SY5Y neuroblastoma cells. We find that Mn dose showed widespread effects in abundance of protein coding genes for metabolism of reactive oxygen species, energy sensing, glycolysis, protein homeostasis including the unfolded protein response and transcriptional regulation. Adaptive responses at physiological Mn concentration-10 µM Mn for 5 h, a concentration that did not result in cell death after 24 h increased abundance of differentially expressed genes (DEGs) in the protein secretion pathway that function in protein trafficking and cellular homeostasis.These include BET1 (Golgi vesicular membrane trafficking protein), ADAM10 (ADAM metallopeptidase domain 10) and ARFGAP3 (ADP-ribosylation factor GTPase activating protein 3). In contrast, 5 h exposure to 100 µM Mn, a concentration that caused cell death after 24 h, increased abundance of DEGs for components of the mitochondrial oxidative phosphorylation pathway. In conclusion, this study provides a framework for Mn dose dependent exposure in a human in vitro cell culture model and provides a testable hypothesis for in vivo studies. Importantly, the transcriptome responses at toxic Mn dose demonstrated patterns observed with neurological diseases and suggest that differential functions of the secretory pathway and mitochondria could provide a basis to improve detection and management of adverse environmental and occupational Mn exposures. Overall design: Examination of transcriptomic responses to Mn dose (0,1,5,10,50,100 µM MnCl2 for 5 h) in human SH-SY5Y neuroblastoma cells with three biological replicates per Mn treatment using Illumina HiSeq 2500.
Transcriptome Analysis Reveals Distinct Responses to Physiologic <i>versus</i> Toxic Manganese Exposure in Human Neuroblastoma Cells.
Specimen part, Cell line, Subject
View SamplesExpression profiling analyses for 5 maize inbreds and 4 hybrids, chosen to represent diversity in genotypes and heterosis responses, revealed a correlation between genetic diversity and transcriptional variation. The majority of differentially expressed genes in each of the different hybrids exhibited additive expression patterns, and ~25% exhibited statistically significant non-additive expression profiles. Among the non-additive profiles, ~80% exhibited hybrid expression levels between the parental levels, ~20% exhibited hybrid expression levels at the parental levels and ~1% exhibited hybrid levels outside the parental range. These findings indicate that the frequencies of additive and non-additive expression patterns are very similar across a range of hybrid lines.
Gene expression analyses in maize inbreds and hybrids with varying levels of heterosis.
No sample metadata fields
View SamplesExpression profiling analyses for eight maize inbreds reveals extensive transcriptional variation. Many genes exhibit presence-absence variation among the inbred lines.
Gene expression analyses in maize inbreds and hybrids with varying levels of heterosis.
No sample metadata fields
View SamplesOBJECTIVE: 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 SamplesThis SuperSeries is composed of the SubSeries listed below.
A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.
Specimen part
View SamplesThe fusion oncoprotein EWS-FLI1 arises from a t(11;22)(q24;q12) chromosomal translocation and causes Ewing's Sarcoma, a malignant bone tumor. The mechanism whereby EWS-FLI1 transforms cells is unknown. Somatic, mosaic expression of human EWS-FLI1 in zebrafish from the heat shock promoter [Tg(HSP:EWS-FLI1)] caused small round blue cell tumors (SRBCTs) similar to human Ewing's sarcoma.
A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.
Specimen part
View SamplesThe fusion oncoprotein EWS-FLI1 arises from a t(11;22)(q24;q12) chromosomal translocation and causes Ewing's Sarcoma, a malignant bone tumor. The mechanism whereby EWS-FLI1 transforms cells is unknown. We made germline transgenic zebrafish expressing human EWS-FLI1 under the control of the heat shock promoter. Induction of EWS-FLI1 expression causes multiple defects in embryonic development.
A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.
Specimen part
View SamplesExpression profiling of Rag2-deficient Ets1++ and Rag2-deficient Ets1-- mature NK cells and WT bone marrow progenitors, WT T cells, and WT Pro B cells
Gene deregulation and chronic activation in natural killer cells deficient in the transcription factor ETS1.
Specimen part
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
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