RNA-seq of mouse neurons in mono-culture and in co-culture with astrocytes, with application of Nrf2 activator tBHQ.
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500
ORGANISM(S): Mus musculus
SUBMITTER: Owen Robert Dando
PROVIDER: E-MTAB-5688 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Grapevine downy mildew is an important disease affecting crop production and causing severe losses. To identify genotype-dependent responses towards this pathogen and to explore the molecular mechanisms involved in grapevine-P. viticola resistance, we have conducted a proteomic analysis of leaf samples from resistant and susceptible grapevine genotypes prior and post-inoculation with the pathogen. Proteins were analyzed by quantitative two-dimensional differential gel electrophoresis (2D-DIGE). The analysis able to identified 50 unique proteins. Functional analysis showed that photosynthesis and metabolism were the main categories differentiating genotypes at 0h and that P. viticola-responsive proteins were mainly involved in photosynthesis, carbohydrate metabolism, stress and defense responses and redox homeostasis. ROS production, total antioxidant capacity and lipid peroxidation on both genotypes were determined and together with the proteome data suggest that Regent presents a strict balance between ROS control and signaling leading to plant cell death activation. Our data reveals the genotype-dependent modulation of plant metabolism and defense responses providing new insights into underlying molecular processes of grapevine resistance against the downy mildew fungus.
2016-12-24 | PXD002920 | Pride
Project description:RNA-Seq analysis of human fibroblasts, induced neurons and cortex from donors of several ages
2015-09-14 | E-MTAB-3037 | biostudies-arrayexpress
Project description:RNA-seq of mouse neurons in mono-culture and in co-culture with neurons, with application of Nrf2 activator tBHQ.
| PRJEB20593 | ENA
Project description:Neurons are almost exclusively cultured in media containing glucose at much higher concentration than found in the brain. To test whether “standard” hyperglycaemic culture conditions affect neuronal respiration compared to near- euglycemic conditions, we grew neuronal cultures with minimal glial contamination from hippocampus and cortex of neonatal C57bl6 mice in standard commercially available media (25 mM Glucose) and in identical media with 5 mM glucose. Neurons grew well in both glucose concentrations until at least 14 days in vitro, with similar morphology and synaptogenesis. Neurons grown in high glucose were more dependent on glycolysis as their primary source of ATP, measured using ATP luminescence and cellular respirometry assays. In contrast, neurons grown in 5 mM glucose showed a more balanced dependence on glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) and greater reserve mitochondrial respiration capacity, relative to standard media. Changes in gene and protein expression levels corroborate these changes in function. Our results suggest that neurons cultured in high glucose media preferentially use glycolysis, opposite to what is known for neurons in vivo as the primary pathway for ATP maintenance. We suggest using neuronal culture systems in 5 mM glucose to better represent physiologically relevant neuronal respiration.
2025-06-30 | PXD059008 | Pride
Project description:We report a transcriptomic analysis from tBHQ (terc-butyl-hydroquinone) treated mice. Mice were treated with this chemical for 20 days using 1.5% mixed in food and allowed water and food ad libitum. After the treatment period, spleen of tBHQ treated and control animals were taken out and CD4+ cells were isolated. Isolated RNA from these cells were subjected to cDNA microarray analysis. Our results show, that tBHQ changes the gene expression of many genes which are involved in metabolic and immune processes. In parallel with transcriptomic analysis, the effect of tBHQ on T cell differentiation was studied. Our results show, that beside changing the gene expression of many genes, tBHQ sensitize effector T cells (Th1, Th2, Th17) and inhibit Treg cells upon stimulation with chemicals.
2017-05-23 | GSE99152 | GEO
Project description:Mutations in the acid β-glucocerebrosidase (GBA1) gene, responsible for the lysosomal storage disorder Gaucher’s disease (GD), are the strongest genetic risk factor for Parkinson’s disease (PD) known to date. To elucidate the mechanisms underlying neurodegeneration in these patients, we generated induced pluripotent stem cells from subjects with GD and PD harboring GBA1 mutations and differentiated them to midbrain dopaminergic neurons. Highly enriched neurons showed a reduction of glucocerebrosidase activity and protein levels, increased glucosylceramide and α-synuclein levels and autophagic/lysosomal defects. Quantitative proteomics profiling revealed an increase of the neuronal calcium-binding protein 2 (NECAB2) in diseased neurons. We found dysregulation of calcium homeostasis and increased vulnerability to stress responses involving elevation of cytosolic calcium in mutant neurons. Importantly, correction of the mutations rescued such pathological phenotypes. Our findings provide evidence for a link between GBA1 mutations and complex changes in autophagic/lysosomal system and intracellular calcium homeostasis, which underlie vulnerability to neurodegeneration.
2014-06-03 | PXD000866 | Pride
Project description:Tert-Butylhydroquinone (tBHQ), a preservative used to prevent oxidative deterioration of oil, fat, and meat products, has been linked to both chemoprotective and adverse effects. This study investigates the impact of chronic dietary tBHQ on survival, growth parameters, organ development, and gene expression in zebrafish (Danio rerio). As tBHQ activates the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2a), a zebrafish line with a mutation in the DNA-binding domain was used to identify Nrf2a-dependent vs. independent effects. Homozygous Nrf2a wildtype (wt) and mutant (m) larvae were fed a diet containing 5% tBHQ or a control diet. Survival and growth parameters were assessed at 15 days and at 5 months, and samples collected for RNA sequencing at 5 months. Chronic dietary exposure to tBHQ throughout the larval and juvenile periods negatively impacted growth and survival. RNA-seq analysis found differentially expressed genes related to growth and development and upregulation of several immune pathways. The findings herein demonstrate that chronic dietary tBHQ exposure may impair growth and survival in both Nrf2a dependent and independent manners.
2023-05-31 | GSE220834 | GEO
Project description:Human SGBS preadipocytes were differentiated into adipocytes, and human iPSCs were differentiated into hypothalamic neurons. Cells were collected for RNA-seq at several differentiation stages. The differentiations were performed in one biological replicate, with three technical replicates (different wells of the differentiation that were also processed individually during library preparation). SGBS Day0: Represents the preadipocyte state. SGBS Day2: Represents immature adipocytes. SGBS Day8: Represents early mature adipocytes. SGBS Day16: Represents mature adipocytes. Hypothalamic Day 12: Represents early hypothalamic neurons. Hypothalamic Day 16: Represents mid hypothalamic neurons. Hypothalamic Day 27: Represents mature hypothalamic neurons.
2021-05-22 | E-MTAB-10461 | biostudies-arrayexpress
Project description:The ability to form memories is a prerequisite for an organismâs behavioural adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell-types, and three time-points before and after contextual learning. Here we show that histone modifications predominantly change during memory acquisition and correlate surprisingly little with changes in gene expression. While long-lasting changes are almost exclusive to neurons, learning-related histone modification and DNA methylation changes occur also in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provides evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring. We examined chromatin modification changes in two distinct mouse brain regions (CA1 and ACC), two cell-types (neurons, non-neurons), and three time-points before and after contextual learning (naive, 1h, 4w).
2015-11-24 | E-GEOD-74965 | biostudies-arrayexpress
Project description:Kabuki Syndrome (KS) is a multisystemic rare disorder, characterized by growth delay, distinctive facial features, intellectual disability, and rarely autism spectrum disorder. This condition is mostly caused by de novo mutations of KMT2D, encoding a catalytic subunit of the COMPASS complex involved in enhancer regulation. KMT2D catalyzes the deposition of histone-3-lysine-4 mono-methyl (H3K4Me1) that marks active and poised enhancers. To assess the impact of KMT2D mutations in the chromatin landscape of KS tissues, we have generated patient-derived induced pluripotent stem cells (iPSC), which we further differentiated into neural crest stem cells (NCSC), mesenchymal stem cells (MSC) and cortical neurons (iN). In addition, we further collected blood samples from 5 additional KS patients. To complete our disease modeling cohort we generated an isogenic KMT2D mutant line from human embryonic stem cells, which we differentiated into neural precursor and mature neurons. Micro-electrode-array (MEA)-based neural network analysis of KS iNs revealed an altered pattern of spontaneous network-bursts in a Kabuki-specific pattern. RNA-seq profiling was performed to relate this aberrant MEA pattern to transcriptional dysregulations, revealing that dysregulated genes were enriched for neuronal functions, such as ion channels, synapse activity, and electrophysiological activity. Here we show that KMT2D haploinsufficiency tends to heavily affect the transcriptome of cortical neurons and differentiated tissues while sparing multipotent states, suggesting that KMT2D has a most prevalent role in terminally differentiated cell and activate transcriptional circuitry unique to each cell type. Moreover, thorough profiling of H3K4Me1 unveiled the almost complete uncoupling between this chromatin mark and the regulatory effects of KMT2D on transcription, which is instead reflected by a defect of H3K27Ac. By integrating RNA-seq with ChIP-seq data we defined TEAD and REST as the master effectors of KMT2D haploinsufficiency. Also, we identified a subset of genes whose regulation is controlled by the balance between KMT2D and EZH2 dosage. Finally, we identified the bona fide direct targets of KMT2D in healthy and KS mature cortical neurons and TEAD2 as the main proxy of KMT2D dysregulation in KS. Overall, our study provides the transcriptional and epigenomic characterization of patient-derived tissues as well as iPSCs and differentiated disease-relevant cell types, as well as the identification of KMT2D direct target in cortical neurons, together with the identification of a neuronal phenotype of the spontaneous electrical activity.
2022-12-25 | E-MTAB-10244 | biostudies-arrayexpress