We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice.
Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: comparison with immune activation.
Age, Specimen part
View SamplesThymic antigen-presenting cells (APCs), including thymic dendritic cells (t-DCs) and medullary thymic epithelial cells (mTECs) have been described to play a critical role in thymic Treg generation. Our findings could show that both these thymic APCs can induce a more pronounced demethylation of Foxp3 and other Treg-specific epigenetic signature genes in developing Tregs when compared to splenic DCs. In order to elucidate the unique properties of thymic APCs, gene expression profiling was performed in comparison to splenic DCs. Transcriptome analysis of thymic APCs revealed differential expression of costimulatory molecules that could be involved in stable Treg generation. Importantly, both mTEC- and t-DC- induced alloantigen-specific Tregs displayed significantly higher efficacy in prolonging skin allograft acceptance when compared to alloantigen-specific Tregs generated by splenic DCs. Overall design: Thymic APCs, including mTECs and t-DCs and splenic DCs were isolated ex vivo from thymus as CD45-EpCAM+Ly51- (mTECs) and CD45+EpCAM-CD11chiLin- (t-DCs) and from spleen as CD11chiLin- (splenic DCs) (Lin is defined as CD90, CD49b, F4/80 and CD19), respectively.
Unique properties of thymic antigen-presenting cells promote epigenetic imprinting of alloantigen-specific regulatory T cells.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Specimen part
View SamplesGerman landrace gilts were fed a high protein diet (HP, 30% CP) throughout their whole pregnancy. Subsequently hepatic transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Specimen part
View SamplesGerman landrace gilts were fed an adequate protein diet (AP, 12% CP) throughout their whole pregnancy. Subsequently hepatic transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn).
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Specimen part
View SamplesGerman landrace gilts were fed a high protein diet (HP, 30% CP) throughout their whole pregnancy. Subsequently muscle transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Specimen part
View SamplesGerman landrace gilts were fed a low protein diet (LP, 6% CP) throughout their whole pregnancy. Subsequently muscle transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Specimen part
View SamplesGerman landrace gilts were fed an adequate protein diet (AP, 12% CP) throughout their whole pregnancy. Subsequently muscle transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Specimen part
View SamplesRett syndrome is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MECP2), an epigenetic regulator of mRNA transcription. Here we report a test of the hypothesis of shared pathophysiology of Rett syndrome and fragile X, another monogenic cause of autism and intellectual disability. In fragile X, the loss of the mRNA translational repressor FMRP leads to exaggerated protein synthesis downstream of metabotropic glutamate receptor 5 (mGluR5). We found that mGluR5- and protein synthesis-dependent synaptic plasticity is similarly altered in area CA1 of Mecp2 KO mice. CA1 pyramidal cell-type-specific, genome-wide profiling of ribosome-bound mRNAs was performed in wild-type and Mecp2 KO hippocampal CA1 neurons to reveal the MeCP2-regulated 'translatome'. We found significant overlap between ribosome-bound transcripts overexpressed in the Mecp2 KO and FMRP mRNA targets. These tended to encode long genes that are functionally related to either cytoskeleton organization or the development of neuronal connectivity. In the Fmr1 KO mouse, chronic treatment with mGluR5 negative allosteric modulators (NAMs) has been shown to ameliorate many mutant phenotypes by correcting excessive protein synthesis. In the Mecp2 KO mice we found that mGluR5 NAM treatment significantly reduces the level of overexpressed ribosome-associated transcripts, particularly those that are also FMRP targets. Some Rett phenotypes were also ameliorated by treatment, most notably hippocampal cell size and life span. Together, these results suggest a potential mechanistic link between MeCP2-mediated transcription regulation and mGluR5/FMRP-mediated protein translation regulation through co-regulation of a subset of genes relevant to synaptic functions. Overall design: TRAP-seq analysis of the effect of negative modulator of mGluR5 on the CA1 neurons (marked by Cck-EGFP-L10a) of a mouse model of Rett syndrome
Negative Allosteric Modulation of mGluR5 Partially Corrects Pathophysiology in a Mouse Model of Rett Syndrome.
Specimen part, Cell line, Treatment, Subject
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