Schizophrenia is a complex psychiatric disorder encompassing a range of symptoms and etiology dependent upon the interaction of genetic and environmental factors. Several risk genes, such as DISC1, have been associated with schizophrenia as well as bipolar disorder (BPD) and major depressive disorder (MDD), consistent with the hypothesis that a shared genetic architecture could contribute to divergent clinical syndromes. The present study compared gene expression profiles across three brain regions in post-mortem tissue from matched subjects with schizophrenia, BPD or MDD and unaffected controls. Post-mortem brain tissue was collected from control subjects and well-matched subjects with schizophrenia, BPD, and MDD (n=19 from each group). RNA was isolated from hippocampus, Brodmann Area 46, and associative striatum and hybridized to U133_Plus2 Affymetrix chips. Data were normalized by RMA, subjected to pairwise comparison followed by Benjamini and Hochberg False Discovery Rate correction (FDR). Samples derived from patients with schizophrenia exhibited many more changes in gene expression across all brain regions than observed in BPD or MDD. Several genes showed changes in both schizophrenia and BPD, though the magnitude of change was usually larger in schizophrenia. Several genes that have variants associated with schizophrenia were found to have altered expression in multiple regions of brains from subjects with schizophrenia. Continued evaluation of circuit-level alterations in gene expression and gene-network relationships may further our understanding of how genetic variants may be influencing biological processes to contribute to psychiatric disease.
STEP levels are unchanged in pre-frontal cortex and associative striatum in post-mortem human brain samples from subjects with schizophrenia, bipolar disorder and major depressive disorder.
Sex, Age, Specimen part, Disease, Disease stage, Race
View SamplesChronic high-sugar feeding (1 M or 34% sucrose) leads to hyperglycemia, obesity, and insulin resistance in adult flies, compared with those fed a control diet (0.15 M or 5% sucrose). We compared two days and four weeks of high-sugar feeding to look at short- and long- term effects on gene expression.
A Complex Relationship between Immunity and Metabolism in Drosophila Diet-Induced Insulin Resistance.
Sex
View SamplesWe characterized insulin receptor (InR)-dependent gene expression in the Drosophila fat body using transgenic RNAi. Chronic knockdown of InR in the fat body was elicited via (r4-GAL4, UAS-InRi) and RNA-seq was used to identify potential target genes. Overall design: Drosophila were reared on control (0.15 M sucrose) or high sugar (0.7 M sucrose) diets until the wandering third instar stage. Control (r4-GAL4 x w1118) offspring were compared with InRi (r4-GAL4 x UAS-InRi) using the VDRC''s w1118 (#60000) or UAS-RNAi targeting InR (#992). Fat bodies were isolated, and RNA was extracted to determine the effects of reduced insulin signaling on gene expression using Illumina RNA-seq.
A Complex Relationship between Immunity and Metabolism in Drosophila Diet-Induced Insulin Resistance.
Sex, Specimen part, Treatment, Subject
View SamplesPurpose: Next-generation sequencing (NGS) provides for quantitation of RNA abundances and comparison of RNA abundances within tissues and cells in a manner not possible with previous microarray technologies. We have made widespread use of Illumina sequencing technologies for RNA quantitation in several publications involving mouse hearts, dating from 2010, and wish to share both high-quality raw sequencing data and data processed to quantitate mRNA abundances from wild-type mice, male and female, at a variety of ages. These data will provide a resource for investigators using microarrays to understand the concentration of transcripts of interest relative to other cardiac RNAs, and will permit deeper interpretation of previous microarray studies. Overall design: 39 cardiac small RNA (microRNA) profiles of 4- to 16 week-old FVB/NJ wild type (WT) mice were generated on Illumina HiSeq 2000 instruments.
Great Expectations: MicroRNA-30d and Cardiac Resynchronization Therapy.
No sample metadata fields
View SamplesAdult mice bearing homozygous floxed Parkin alleles (PMIDs 15249681, 21376232; T M Dawson), with or without the Myh6-driven MERCreMER transgene, were administered tamoxifen at 6-10 wks of age. Tissues were obtained from euthanized mice 9-10 weeks after tamoxifen induction. Overall design: 6 floxed, non-Cre (noninduced) mouse hearts; 6 floxed, MERCreMer, adult-induced, Parkin knockout mouse hearts
Central Parkin: The evolving role of Parkin in the heart.
Specimen part, Subject, Time
View SamplesDysfunctional Parkin-mediated mitophagic culling of senescent or damaged mitochondria is a major pathological process underlying Parkinson disease and a potential genetic mechanism of cardiomyopathy. Despite epidemiological associations between Parkinson disease and heart failure, the role of Parkin and mitophagic quality control in maintaining normal cardiac homeostasis is poorly understood.We used germline mutants and cardiac-specific RNA interference to interrogate Parkin regulation of cardiomyocyte mitochondria and examine functional crosstalk between mitophagy and mitochondrial dynamics in Drosophila heart tubes. Overall design: 5 wild-type mouse hearts; 4 germline Parkin knockout mouse hearts Please note that the mouse cardiac examples were an adjunct to the Drosophila studies that comprised most of the associated publication. However, mRNA-sequencing was only performed on the mouse samples, not the Drosophila heart tubes.
Central Parkin: The evolving role of Parkin in the heart.
Specimen part, Subject
View SamplesPurpose: Next-generation sequencing (NGS) provides for quantitation of RNA abundances and comparison of RNA abundances within tissues and cells in a manner not possible with previous microarray technologies. We have made widespread use of Illumina sequencing technologies for RNA quantitation in several publications involving mouse hearts, dating from 2010, and wish to share both high-quality raw sequencing data and data processed to quantitate mRNA abundances from wild-type mice, male and female, at a variety of ages. These data will provide a resource for investigators using microarrays to understand the concentration of transcripts of interest relative to other cardiac RNAs, and will permit deeper interpretation of previous microarray studies. Overall design: 6 cardiac small RNA (microRNA) profiles of 18 week-old C57BL/6J wild type (WT) mice were generated on Illumina HiSeq 2000 instruments.
Menage a Trois: intimate relationship among a microRNA, long noncoding RNA, and mRNA.
No sample metadata fields
View SamplesPurpose: Next-generation sequencing (NGS) provides for quantitation of RNA abundances and comparison of RNA abundances within tissues and cells in a manner not possible with previous microarray technologies. We have made widespread use of Illumina sequencing technologies for RNA quantitation in several publications involving mouse hearts, dating from 2010, and wish to share both high-quality raw sequencing data and data processed to quantitate mRNA abundances from wild-type mice, male and female, at a variety of ages (see our FVB/NJ data submission). These data will provide a resource for investigators using microarrays to understand the concentration of transcripts of interest relative to other cardiac RNAs, and will permit deeper interpretation of previous microarray studies. Overall design: 4 cardiac polyA+-RNA profiles of 12 week-old C57BL/6J wild type (WT) mice were generated on Illumina HiSeq 2000 instruments.
Menage a Trois: intimate relationship among a microRNA, long noncoding RNA, and mRNA.
No sample metadata fields
View SamplesRationale: MicroRNAs play key roles in hypertrophic stress responses. miR-378(-3p) is a highly abundant, cardiomyocyte-enriched microRNA whose downregulation in pressure-overload has been suggested as detrimental to the heart. Previous studies have utilized systemic anti-miR or microRNA-encoding virus administration, and thus questions regarding the cardiomyocyte-autonomous roles of miR-378 remain. Objective: To examine whether persistent overexpression of miR-378 in cardiomyocytes alters the phenotype of the unstressed heart, whether its overexpression is beneficial or deleterious in the setting of pressure-overload, and to comprehensively identify its cardiomyocyte-specific effects on mRNA regulation. Methods and Results: Cardiac function was compared in young (10-12 week-old) mice overexpressing miR-378 in the heart under the control of the Myh6 promoter (alphaMHC-miR-378 mice), in older (40 week-old) mice and their age-matched wild-type controls. Older alphaMHC-miR-378 mice exhibited decreased fractional shortening and modest chamber dilation with an increase in cardiomyocyte length. When subjected to pressure-overload, cardiomyocyte length was increased in young alphaMHC-miR-378 mice, but fractional shortening declined precipitously over two weeks. Transcriptome profiling of wild-type and alphaMHC-miR-378 hearts in unstressed and pressure-overload conditions revealed dysregulation of several upstream metabolic and mitochondrial genes in alphaMHC-miR-378 hearts, compromising the reprogramming that occurs during early adaptation to pressure overload. Ago2 immunoprecipitation with mRNA sequencing revealed novel miR-378 cardiac mRNA targets including Akt1 and Epac2 and demonstrated the contextual nature of previously described miR-378 targeting events. Conclusions: Long-term upregulation of miR-378 levels in the heart is not innocuous and exacerbates contractile dysfunction in pressure-overload hypertrophy through numerous signaling mechanisms. Overall design: Cardiac polyadenylated RNA (mRNA) or RISC-seq (total RNA-seq of Ago2 immunoprecipitate) profiles were generated from nontransgenic and transgenic mouse hearts of FVB/N background, on Illumina HiSeq 2000 instruments. Male mice 8-12 weeks of age were used in these studies, and subjected to sham surgery or 2 weeks of pressure-overload via transverse aortic constriction (TAC). 3 nontransgenic sham, 3 transgenic sham, 7 nontransgenic TAC, 7 transgenic TAC, each with mRNA-seq and RISC-seq data.
Cardiac Disease Status Dictates Functional mRNA Targeting Profiles of Individual MicroRNAs.
No sample metadata fields
View SamplesmiR-133a-3p is a highly abundant cardiomyocyte-enriched microRNA whose expression is persistently decreased in response to pressure overload (or transverse aortic constriction, TAC) in mice. Overexpression of miR-133a in cardiomyocytes of mouse hearts in vivo (under the control of the Myh6 promoter) decreases pressure overload-induced apoptosis and fibrosis. In previous studies using microarray platforms, we detected numerous mRNAs whose transcript levels were altered by either or both of miR-133a overexpression and pressure overload. The data set presented here builds upon our previous study in these mice by examining mRNA-RISC associations (using Ago2-immunoprecipitated RNA) and global mRNA abundances via RNA-sequencing procedures, and tests the hypothesis that mRNAs targeted by overexpressed miR-133a are dissimilar between sham and TAC contexts. Overall design: Cardiac polyadenylated RNA (mRNA) profiles were generated from nontransgenic and transgenic mouse hearts of FVB/N background, on Illumina HiSeq 2000 instruments. Male mice 8-12 weeks of age were used in these studies, and subjected to sham surgery or 1 week of pressure-overload via transverse aortic constriction (TAC). 3 nontransgenic sham, 7 transgenic sham, 5 nontransgenic TAC, 4 transgenic TAC, each with mRNA-seq and RISC-seq (mRNA-seq of Ago2 immunoprecipitate) data.
Cardiac Disease Status Dictates Functional mRNA Targeting Profiles of Individual MicroRNAs.
No sample metadata fields
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