See "Akula et al., Molecular Psychiatry in Press". RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality post-mortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false-discovery rate of <5%, we detected 5 differentially-expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, PROM1/CD133 and ABCG2 play important roles in neuroplasticity. We also show for the first time differential expression of long non-coding RNAs (lncRNAs) in BD. DE transcripts include those of SRSF5 and RFX4, which along with lncRNAs play a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology (GO) categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies. Overall design: Brain transcriptome in bipolar disorder
RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms and GTPase binding in bipolar disorder.
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View SamplesImpairments in certain cognitive processes (e.g., working memory) are typically most pronounced in schizophrenia (SZ), intermediate in bipolar disorder (BP) and least in major depressive disorder (MDD).
Transcriptome Alterations in Prefrontal Pyramidal Cells Distinguish Schizophrenia From Bipolar and Major Depressive Disorders.
Specimen part
View SamplesThe goal of this study is to simultaneously interrogate the gene expression programs in human host cells (human foreskin fibroblasts) infected with the intracellular parasite Trypanosoma cruzi. We conducted high-resolution sequencing of the transcriptomes of T. cruzi and infected human foreskin fibroblasts (HFFs) using an RNA-seq approach. An array of computational tools was applied to map reads to the T. cruzi and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for T. cruzi genes at at various time points post-infection enabling us to identify co-expression patterns that correlate with the biology of the parasite. We also conducted a time course of infection in host cells to obtain a preliminary analysis of the dynamic nature of parasite and host cell gene expression programs in the context of infection. These data provide the first glimpse of T. cruzi gene expression programs that are uniquely activated in the context of intracellular infection along with the transcriptional response of the human host cell. The study provides a solid framework for future functional and genomic studies of Chagas disease as well as intracellular pathogenesis in general.
Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during Intracellular Infection.
No sample metadata fields
View SamplesEbf genes regulate differentiation of several cell type. Ebf2 is expressed in Schwann cells and Ebf2-/- mice show among other phenotypical abnormalities a delay in the onset of myelination associated to a decreased expression of genes regulating myelination. In addition at one month of age Ebf2-/- mice show decreased motor conduction velocity and morphological alteration in sciatic nerves. Ebf2 target genes are unknown. To identify Ebf2 target genes with a role in myelination, we compared the expression profiles of sciatic nerves isolated from P2 Wt and Ebf2-/- mice by microarray analysis.
The Transcription Factors EBF1 and EBF2 Are Positive Regulators of Myelination in Schwann Cells.
Age, Specimen part
View SamplesSchizophrenia is associated with alterations in working memory that reflect dysfunction of dorsolateral prefrontal cortex (DLPFC) circuitry. Working memory depends on the activity of excitatory pyramidal cells in DLPFC layer 3, and to a lesser extent in layer 5.
Distinctive transcriptome alterations of prefrontal pyramidal neurons in schizophrenia and schizoaffective disorder.
Specimen part
View SamplesRed light can affect a variety of responses in Arabidopsis. We characterize the early gene expression patterns of seedlings exposed to 1 hour of red light using a small sized sample of 5, 7-day-old seedlings and also performed dark controls.
Extraction and labeling methods for microarrays using small amounts of plant tissue.
No sample metadata fields
View SamplesThis study analyzes transcriptome profiles in pre-germinated seeds and hypoxia-treated seedlings of Arabidopsis thaliana wild type (Col-0) and homozygous mutants (prt6-1 and ate1 ate2). This dataset includes CEL files, RMA signal values and MAS5 P/M/A calls. For pre-germinated seeds, seeds imbibed for 24 h were used for total RNA extraction. For hypoxia treatment, 7-d-old seedlings were incubated in a hypoxia chamber for 2 h and the entire seedling was subjected to RNA extraction. Quantitative profiling of cellular mRNAs was accomplished with the Affymetrix ATH1 platform. Changes in the transcriptome during early seed germination stage and in response to hypoxia in seedlings were evaluated. The data led to identification of mRNAs with abundance regulated by PRT6 and ATE1 / ATE2, which are essential components for the N-end rule pathway of targeted proteolysis (NERP). A combination of genetic, biochemical and molecular analyses reveal that NERP coordinates the stability of key ethylene responsive factor (ERF) family transcription factors, which regulate expression of core hypoxia response genes and tolerance to low oxygen stress. This indicates that the NERP functions as a homeostatic sensor of low oxygen in plants.
Homeostatic response to hypoxia is regulated by the N-end rule pathway in plants.
Age, Specimen part, Treatment
View SamplesOligodendrocyte dysfunction underlies many neurological disorders but rapid assessment of mutation-specific effects in these cells has been impractical. To enable functional genetics in oligodendrocytes, here we report a highly efficient method for generating oligodendrocytes and their progenitors from mouse embryonic and induced pluripotent stem cells, independent of mouse strain or mutational status. We demonstrate that this approach, when combined with genome engineering, provides a powerful platform for the expeditious study of genotype-phenotype relationships in oligodendrocytes. Overall design: Cells were lysed directly in 1 ml of TRIzol (Thermo Fisher) and stored at -80°C. Once all samples were collected, samples were thawed on ice and RNA was separated with chloroform using Phase Lock Gel tubes (5prime). RNA was isolated using the miRNeasy Mini Kit (Qiagen) according to the manufacture's protocol. One microgram of each sample was then subject to ribosome depletion, fragmented, and library prepared using the TruSeq Stranded Total RNA Kit with Ribo Zero Gold (Illumina) according to the manufacturer's protocol and indexed using TruSeq adapters. One hundred base pair paired-end reads were generated for each sample on the Illumina HiSeq 2500 (Case Western Reserve University Sequencing Core; Cleveland, OH). Samples include mESC derived oligodendrocyte progenitor cells (OPCs) from four different wildtype mouse strains at 0 hr, 24, hr, 48 hr, and 72 hr after treatment with thyroid hormone T3 (n = 4 biological replicates per time point). Two additional samples include mutant OPCs (shiverer and MYRF knockout ''delMYRF'') at 72 hr time point.
Rapid functional genetics of the oligodendrocyte lineage using pluripotent stem cells.
Specimen part, Cell line, Subject
View Samples2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a large number of biological effects, including skin, cardiovascular, neurologic disease, diabetes, infertility and cancer. We analysed the in vitro TCDD effects on human CD34+ cells and tested the gene expression modulation by means of microarray analyses before and after TCDD exposure. We identified 253 differentially modulated probe sets, identifying 217 well-characterized genes. A large part of these were associated with cell adhesion and/or angiogenesis and with transcription regulation. Synaptic transmission and visual perception functions, with the particular involvement of the GABAergic pathway, were also significantly modulated. Numerous transcripts involved in cell cycle or cell proliferation, immune response, signal transduction, ion channel activity or calcium ion binding, tissue development and differentiation, female or male fertility or in several metabolic pathways were also affected after dioxin exposure. The transcriptional profile induced by TCDD treatment on human CD34+ cells strikingly reproduces the clinical and biological effects observed in individuals exposed to dioxin and in biological experimental systems.
Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects.
Specimen part, Treatment
View SamplesThese investigations studied the fundamentals of how plants perceive gravity and develop in microgravity. It informs how gene regulation is altered by spaceflight conditions.
Comparative transcriptomics indicate changes in cell wall organization and stress response in seedlings during spaceflight.
Specimen part
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