A fundamental question in biology is how gene expression is regulated to give rise to a phenotype. However, transcriptional variability is rarely considered and could influence the relationship between genotype and phenotype. It is known in unicellular organisms that gene expression is often noisy rather than uniform and has been proposed to be beneficial when environmental conditions are unpredictable. However, little is known about transcriptional variability in multicellular organisms. Using transcriptomic approaches, we analysed gene expression variability over a 24 hours time-course between individual Arabidopsis thaliana plants growing in stable conditions. We identified hundreds of genes that exhibit high inter-individual variability and found that many are involved in environmental responses. We also identified factors that might facilitate gene expression variability, such as gene size, the number of transcription factors regulating a gene and the chromatin environment. These results will bring a new light into the impact of transcriptional variability in gene expression regulation in plants. Overall design: RNA-seq were generated for 14 individual seedlings for each of the 12 following time points: ZT2, ZT4, ZT6, ZT8, ZT10, ZT12 (just before dusk), ZT14, ZT16, ZT18, ZT20, ZT22 and ZT24 (just before dawn).
Widespread inter-individual gene expression variability in <i>Arabidopsis thaliana</i>.
Specimen part, Subject, Time
View SamplesPTEN is thought to play a critical role in T cell activation by negatively regulating the PI3K signaling pathway important for cellular activation, growth, and proliferation. T cells from mice in which PTEN was conditionally deleted in the thymus were reported to display CD28-independent IL-2 production and relative resistance to anergy induction. However, such observations could have stemmed from alterations in T cell development due to early deletion in thymocytes. To directly eliminate PTEN in post-thymic T cells, we utilized CAR Tg x PTENflox/flox mice which enabled gene deletion using a Cre adenovirus in vitro. Gene expression profiling revealed a small subset of induced genes that were augmented upon PTEN deletion and T cell stimulation. Our results indicate that deletion of PTEN can augment the activation of post-thymic T cells. Nonetheless, PTEN inhibition may be a viable target for immune potentiation due to increased cytokine production by activated CD4+ cells.
Conditional deletion of PTEN in peripheral T cells augments TCR-mediated activation but does not abrogate CD28 dependency or prevent anergy induction.
Specimen part
View SamplesBipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (dorsolateral prefrontal cortex and orbitofrontal cortex) from patients with bipolar disorder and matched healthy controls.
Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.
Sex, Age, Disease
View SamplesBipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (dorsolateral prefrontal cortex) from patients with bipolar disorder and matched healthy controls. A cohort of 70 subjects was investigated and the final analysis included 30 bipolar and 31 control subjects. Differences between disease and control groups were identified using a rigorous statistical analysis with correction for confounding variables and multiple testing.
Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.
Sex, Age, Disease
View SamplesFresh frozen post mortem prefrontal cortex tissue (Brodman area 46) was obtained from 44 individuals varying in age from 0 to 49 years. RNA was extracted from these samples and hybridized to HG133plus2.0 GeneChips. The data was used to examine patterns of gene expression over the course of human postnatal developmental and ageing.
Gene expression in the prefrontal cortex during adolescence: implications for the onset of schizophrenia.
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View SamplesThe tumor suppressor protein 53BP1, a pivotal regulator of DNA double-strand break (DSB) repair, was first identified as a p53-interacting protein over two decades ago, however its direct contributions to p53-dependent cellular activities remain undefined. Here, we reveal 53BP1 stimulates genome-wide p53-dependent gene transactivation and repression events in response to ionizing radiation (IR) and synthetic p53 activation. 53BP1-dependent p53 modulation requires both auto-oligomerization and tandem-BRCT domain mediated bivalent interactions with p53 and the ubiquitin-specific protease USP28. Loss of these activities results in inefficient p53-dependent cell-cycle checkpoint and exit responses. Furthermore, we demonstrate 53BP1-USP28 cooperation to be essential for normal p53-promoter element interactions and gene transactivation-associated events, yet dispensable for 53BP1-dependent DSB repair regulation. Collectively, our data provides a mechanistic explanation for 53BP1-p53 cooperation in controlling anti-tumorigenic cell fate decisions, and reveal these activities to be distinct and separable from 53BP1’s regulation of DNA double-strand break repair pathway choice. Overall design: We evaluated the transcriptional profiles of two 53BP1? cell lines and included a positive (WT) and a negative (p53?) controls. These cell lines were treated with Nutlin-3, ionising radiation or mock treated. Three independent replicates were included for each independent condition generating a total of 36 samples.
53BP1 Integrates DNA Repair and p53-Dependent Cell Fate Decisions via Distinct Mechanisms.
Cell line, Treatment, Subject
View SamplesBipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (orbitofrontal cortex) from patients with bipolar disorder and matched healthy controls. Orbitofrontal cortex tissue from a cohort of 30 subjects was investigated and the final analysis included 10 bipolar and 11 control subjects. Differences between disease and control groups were identified using a rigorous statistical analysis with correction for confounding variables and multiple testing.
Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.
Sex, Age, Disease
View SamplesDown syndrome (DS) is the result of trisomy chromosome 21 but the mechanisms by which the genotype leads to the characteristic disease phenotype are unclear. We performed a microarray study using human adult brain tissue (dorsolateral prefrontal cortex) from DS subjects and healthy controls to characterise for the first time the human adult Down syndrome brain
Gene expression profiling in the adult Down syndrome brain.
Sex, Age, Disease
View SamplesUsing fluorescence activated cell sorting, we isolated CD45+, CSF1R-GFP+, F4/80+, Ly6G- mouse lung monocytes and macrophages at 7 days after pneumonectomy procedure. We then used microfluidic single cell RNA-sequencing to transcriptional profile unique myeloid subsets. Using the pneumonectomy dataset, we identified 6 cell groups and 4 gene groups that marked several regenerative macrophage subsets including CCR2+, Ly6C+ monocytes and CD206+, Chil3+ M2-like macrophages. Overall design: individual macrophages 7 days post-pneumonectomy in a B6 CSF1R-GFP mouse
Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy.
Specimen part, Subject
View SamplesUsing fluorescence activated cell sorting, we isolated CD45+, CSF1R-GFP+, F4/80+, Ly6G- mouse lung monocytes and macrophages at 7 days after sham thoracotomy procedures. We then used microfluidic single cell RNA-sequencing to transcriptional profile unique myeloid subsets. Overall design: After sequencing 31 single cell transcriptomes were analyzed. Hierarcical and k-means clustering reveals several populations of macrophages are present in the lung.
Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy.
Specimen part, Subject
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