IgE plays an essential role in the pathogenesis of allergies and its production is strongly regulated. A transient IgE germinal center phase and lack of IgE memory cells limit the generation of pathogenic IgE, but this can be overcome by sequential switching of IgG1 cells to IgE. We investigated which population of IgG1 cells can give rise to IgE-producing cells in memory responses. We identified three populations of IgG1 memory B cells (DP:CD73+CD80+, SP:CD73-CD80+, DN:CD73-CD80-) that generate IgE plasma cells of high or low affinity, but none gives rise to IgE germinal center cells or IgE memory cells. The two memory IgG1 populations differ however in their ability to differentiate into IgG1 plasma cells and germinal center cells, and to expand the IgG1 memory B cell pool. To explore the molecular mechanisms that may explain the distinct functions of IgG1 memory B cell subsets we compared their expression by transcriptome analysis using next generation sequencing. Overall design: mRNA profiles of quadruplicates of double positive (DP:CD73+CD80+), single positive (SP:CD73-CD80+), double negative (DN:CD73-CD80-) IgG1 memory B cells along with IgG1 germinal center (GC) cells and naïve B cells were generated using Illumina high throughput sequencing.
IgG1 memory B cells keep the memory of IgE responses.
Specimen part, Cell line, Subject
View SamplesWe examined gene expression of LAPC4 cells after knocking down -TrCP, androgen ablation, or the combined treatments compared to non treated cells.
beta-TrCP inhibition reduces prostate cancer cell growth via upregulation of the aryl hydrocarbon receptor.
Cell line
View SamplesTo explore the primary cause of Dilated Cardiomyopathy in heart samples from DCM-diagnosed patients who had undergone heart transplant (hDCM), we set out to identify differentially expressed genes by massively parallel sequencing of heart samples. Overall design: Methods: Heart mRNA profiles from DCM-diagnosed patients who had undergone heart transplant (hDCM) were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence.
No sample metadata fields
View SamplesTo explore the primary cause of Dilated Cardiomyopathy in Bmi1-null mice, we set out to identify differentially expressed genes by massively parallel sequencing of heart samples from Bmi1f/f;aMHCTM-Cretg/+ mice versus aMHCTM-Cretg/+ control mice (17 weeks postinduction). Overall design: Methods: Heart mRNA profiles of 17-weeks post-induction Bmi1f/f; MHCTM-Cretg/+ mice and MHCTM-Cretg/+ control mice were generated by deep sequencing, in triplicate, using Illumina GAIIx. Sequence reads were pre-processed with Cutadapt 1.2.1, to remove TruSeq adapters and mapped on the mouse transcriptome (Ensembl gene-build GRCm38.v70) using RSEM v1.2.3. The Bioconductor package EdgeR was used to normalize data with TMM and to test for differential expression of genes using GLM.
Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence.
No sample metadata fields
View SamplesSadanandam et al. (2013) recently published a study based on the use of microarray data to classify colorectal cancer (CRC) samples. The classification claimed to have strong clinical implications, as reflected in the paper title: A colorectal cancer classification system that associates cellular phenotype and responses to therapy. They defined five subtypes: (i) inflammatory; (ii) goblet-like; (iii) enterocyte; (iv) transit-amplifying; and (v) stem-like. Based on drug sensitivity data from 21 patients, they also reported that the so-called stem-like subtype show differential sensitivity to FOLFIRI. This is the key result in their publication, since it implies a direct relation between the subtype and the choice of CRC therapy (i.e. FOLFIRI response). However, our analyses using the same drug sensitivity data and results from additional patients showed that the CRC classification reported by Sadanandam et al. is not predictive of FOLFIRI response.
Colorectal cancer classification based on gene expression is not associated with FOLFIRI response.
Specimen part
View SamplesSubstantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. However, ventral tegmental area (VTA), a region adjacent to SNpc, is less affected in PD. Until now, molecular mechanisms behind VTA aging have not been fully investigated using high throughput techniques.
Age-mediated transcriptomic changes in adult mouse substantia nigra.
Specimen part
View SamplesSubstantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques.
Age-mediated transcriptomic changes in adult mouse substantia nigra.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Age-mediated transcriptomic changes in adult mouse substantia nigra.
Specimen part
View SamplesImpaired DNA replication is a hallmark of cancer and a cause of genomic instability. We report that, in addition to causing genetic change, impaired DNA replication during embryonic development can have major epigenetic consequences for a genome. In a genome-wide screen, we identified impaired DNA replication as causing increased expression from a repressed transgene in Caenorhabditis elegans. The acquired expression state behaved as an “epiallele,” being inherited for multiple generations before fully resetting. Derepression was not restricted to the transgene but was caused by a global reduction in heterochromatin-associated histone modifications due to the impaired retention of modified histones on DNA during replication in the early embryo. Impaired DNA replication during development can therefore globally derepress chromatin, creating new intergenerationally inherited epigenetic expression states. Overall design: 3 replicates of div-1 mutant worms and N2 wild type worms
Impaired DNA replication derepresses chromatin and generates a transgenerationally inherited epigenetic memory.
Specimen part, Subject
View SamplesTargeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals is proclaimed to have value-added clinical potential in the regeneration of complex cell types like cardiomyocytes. Despite the availability of several small molecule inhibitors capable of modulating specific receptor-ligand interaction or enzymatic activity, no bioactive synthetic DNA-binding inhibitor targeting key cell fate-controlling gene like SOX2 is available yet. Herein, we demonstrate a novel DNA-based chemical approach to guide hiPSCs differentiation using pyrrole-imidazole polyamides (PIPs), which are sequence-selective DNA-binding synthetic molecules. Harnessing the knowledge about key transcriptional changes associated with cardiomyocyte induction, we developed a PIP termed SOX-L targeting 5-CTTTGTT-3 sequence and demonstrate the inhibition of SOX2-DNA interaction and mesoderm induction of hiPSCs. Genome-wide gene analyses revealed that SOX-L remarkably specified cardiac mesoderm by triggering targeted alteration in SOX2-associated gene regulatory networks. Also, employment of SOX-L along with a Wnt inhibitor successfully generated spontaneously contracting cardiomyocytes to validate our concept that DNA-binding inhibitors like PIPs could be used for directed differentiation of hiPSCs. Because PIPs could be fine-tuned to target specific DNA sequences, our DNA-based approach could be expanded to directly target and distinctively regulate key transcription factor associated with the desired cell type.
A synthetic DNA-binding inhibitor of SOX2 guides human induced pluripotent stem cells to differentiate into mesoderm.
Specimen part, Cell line, Treatment, Time
View Samples