This SuperSeries is composed of the SubSeries listed below.
Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy.
Sex, Specimen part
View SamplesWe are using genome-wide ChIP-seq with isoform-specific antibodies and chromatin from select tissues of mice challenged with different dietary conditions that enrich for specific SREBPs.
Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy.
Sex, Specimen part
View SamplesThis study demonstrates quantitative and qualitative differences between type I IFN signatures in autoimmunity and viral infection using purified CD4pos T cells and CD16pos- and CD16neg-monocyte subsets. We were able to discriminate between cell-specific viral response signatures and the pathogenically amplified IFN signatures observed in autoimmunity. The differences were of both a qualitative and quantitative nature, as the signatures in the patients with SLE were characterized by much more complexly compiled gene patterns with increased absolute gene expression levels.
Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference?
Specimen part
View SamplesMany cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as TNF in RA and IFN/ in SLE. To relate the transcriptional imprinting of cytokines in a cell type-specific and disease-specific manner, we generated gene-expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-generated signatures induced by TNF, IFN2a and IFN. Monocytes from SLE and RA patients revealed disease-specific gene-expression profiles. In vitro-generated signatures induced by IFN2a and IFN showed similar profiles that only partially overlapped with those induced by TNF. Comparisons between disease-specific and in vitro-generated signatures identified cytokine-regulated genes in SLE and RA with qualitative and quantitative differences. The IFN-responses in SLE and RA were found to be regulated in a STAT1-dependent and STAT1-independent manner, respectively. Similarly, genes recognized as TNF-regulated were clearly distinguishable between RA and SLE patients. While the activity of SLE monocytes was mainly driven by IFN, the activity from RA monocytes showed a dominance of TNF that was characterized by STAT1 down-regulation. The responses to specific cytokines were revealed to be disease-dependent and reflected the interplay of cytokines within various inflammatory milieus. This study has demonstrated that monocytes from RA and SLE patients exhibit disease-specific gene-expression profiles, which can be molecularly dissected when compared to in vitro-generated cytokine signatures. The results suggest that an assessment of cytokine-response status in monocytes may be helpful for improvement of diagnosis and selection of the best cytokine target for therapeutic intervention.
The multifaceted balance of TNF-α and type I/II interferon responses in SLE and RA: how monocytes manage the impact of cytokines.
Specimen part, Disease, Disease stage, Treatment, Subject
View SamplesHuman engeneered skin carrying GFP positive melanoma cells was transplanted in immunocompromised rats.
low neurotrophin receptor CD271 regulates phenotype switching in melanoma.
Specimen part, Time
View SamplesDnmt3b is a DNA methytransferase which is an enzyme that methylated genomic DNA which contributes to genomic stability and transcriptional regulation.
Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis.
Specimen part, Time
View SamplesThrough genome-wide transcriptional comparisons, this study interrogates the capacity of iPSCs to accurately model pathogenic signatures of structural cardiac defects. Herein, we studied the molecular etiology of structural cardiac defects in Nos3-/- mice via transcriptional analysis of stage-matched embryonic and iPSC-derived tissues. In vitro comparisons of differentiated embryoid bodies were calibrated to in utero benchmarks of health and disease. Integrated systems biology analysis of WT and Nos3-/- transcriptional profiles revealed 50% concordant expression patterns between in utero embryonic and ex vivo iPSC-derived tissue. In particular, up-regulation of glucose metabolism (p-value = 3.95x10-12) and down-regulation of fatty acid metabolism (p-value = 6.71x10-12) highlight a bioenergetic signature of early Nos3 deficiency during cardiogenesis that can be recapitulated in iPSC-derived tissues. The in vitro concordance of early Nos3-/- disease signatures supports the utility of iPSCs as a cell-autonomous model of structural heart defects. Moreover, this study supports the use of iPSCs as a platform to pinpoint initial stages of cardiac pathogenesis.
Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis.
Specimen part, Time
View SamplesThrough genome-wide transcriptional comparisons, this study interrogates the capacity of iPSCs to accurately model pathogenic signatures of structural cardiac defects. Herein, we studied the molecular etiology of structural cardiac defects in Nos3-/- mice via transcriptional analysis of stage-matched embryonic and iPSC-derived tissues. In vitro comparisons of differentiated embryoid bodies were calibrated to in utero benchmarks of health and disease. Integrated systems biology analysis of WT and Nos3-/- transcriptional profiles revealed 50% concordant expression patterns between in utero embryonic and ex vivo iPSC-derived tissue. In particular, up-regulation of glucose metabolism (p-value = 3.95x10-12) and down-regulation of fatty acid metabolism (p-value = 6.71x10-12) highlight a bioenergetic signature of early Nos3 deficiency during cardiogenesis that can be recapitulated in iPSC-derived tissues. The in vitro concordance of early Nos3-/- disease signatures supports the utility of iPSCs as a cell-autonomous model of structural heart defects. Moreover, this study supports the use of iPSCs as a platform to pinpoint initial stages of cardiac pathogenesis.
Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis.
Specimen part
View SamplesConditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency.
Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons.
Specimen part
View Samples