CD25+ regulatory T cells develop in the thymus (nTregs), but may also be generated in the periphery upon stimulation of naive CD4 T cells under appropriate conditions (iTregs). The mechanisms that regulate the generation of peripheral iTregs are largely unknown.
Analysis of the transcriptional program of developing induced regulatory T cells.
Specimen part, Treatment, Subject, Time
View SamplesBasic helix loop helix enhancer 40 (Bhlhe40) is a transcription factor expressed in rodent hippocampus, however, its role in neuronal function is not well understood. Here, we used Bhlhe40 null mice on a congenic C57Bl6/J background (Bhlhe40 KO) to investigate the impact of Bhlhe40 on neuronal excitability and synaptic plasticity. A whole genome expression array predicted that Bhlhe40 KO mice have up-regulated insulin-related pathways and down-regulated neuronal signaling-related pathways in the hippocampus. We validated that insulin degrading enzyme mRNA (Ide) and IDE protein are significantly downregulated in Bhlhe40 KO hippocampi. No significant difference was observed in hippocampal insulin levels. In hippocampal slices, we found CA1 neurons have increased miniature excitatory post-synaptic current (mEPSC) amplitude and decreased inhibitory post-synaptic current (IPSC) amplitude, indicating hyper-excitability in CA1 neurons in Bhlhe40 KO mice. At CA1 synapses, we found a reduction in long term potentiation (LTP) and long term depression (LTD), indicating an impairment in hippocampal synaptic plasticity in Bhlhe40 KO hippocampal slices. Bhlhe40 KO mice displayed no difference in seizure response to the convulsant kainic acid (KA) relative to controls. We found that while Bhlhe40 KO mice have decreased exploratory behavior they do not display alterations in spatial learning and memory. Together this suggests that Bhlhe40 plays a role in modulating neuronal excitability and synaptic plasticity ex vivo, however, Bhlhe40 alone does not play a significant role in seizure susceptibility and learning and memory in vivo. In addition, based on the reduction in IDE protein levels in these mice, there may be dysregulation of other known IDE substrates, namely insulin growth factor (Igf)-1, Igf-2, and Amyloid beta (A).
Mice lacking the transcriptional regulator Bhlhe40 have enhanced neuronal excitability and impaired synaptic plasticity in the hippocampus.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Specimen part, Treatment
View SamplesWe used microarrays to detail the global gene transcription underlying T cells activation during the first 24 hours after stimulation.
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Specimen part, Treatment
View SamplesWe used microarrays to detail the global gene transcription effect of Dec1 underlying T cells activation during the first 24 hours after stimulation.
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Specimen part, Treatment
View SamplesB cells from human tonsil and blood were sorted using flow cytometry. The human samples were processed immediately ex-vivo using markers for known B cell subsets.
Analysis of somatic hypermutation in X-linked hyper-IgM syndrome shows specific deficiencies in mutational targeting.
No sample metadata fields
View SamplesSorted B cells using flow cytometry
Analysis of somatic hypermutation in X-linked hyper-IgM syndrome shows specific deficiencies in mutational targeting.
No sample metadata fields
View SamplesSee "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.
No sample metadata fields
View SamplesThe purpose was to determine AcP- and AcPb-dependent gene responses to IL-1 by virally-reconstituting AcP-deficient mouse embryonic cortical neurons with CD25 (control), full length AcP, AcPb or the combination of both. A control population was transduced with a CD25-expressing virus. Half the samples were stimulated with IL-1-beta for four hours, RNA was analyzed by microarray.
A central nervous system-restricted isoform of the interleukin-1 receptor accessory protein modulates neuronal responses to interleukin-1.
Specimen part
View SamplesIn this experiment, total RNA was extracted from asynchronous population of L1210 cells and hybridized to Affymetrix 430A 2.0 arrays in order to obtain an expression profile of these cells. We have previously mapped the replication timing of the entire mouse genome in this cell line, using mouse CGH arrays (see E-MEXP-1022). We wanted to validate in our system the known correlation between early replication and expression and to analyze its extent. To this end, we have measured the expression in the same cell line (L1210 cells). Two biological replicates were hybridized to 2 identical microarrays. Expression levels were highly similar between the 2 replicates (r=0.98).
Global organization of replication time zones of the mouse genome.
Cell line, Subject
View Samples