This SuperSeries is composed of the SubSeries listed below.
Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins.
Sex, Age, Specimen part
View SamplesMyasthenia gravis (MG) is a relatively rare autoimmune neuromuscular disorder. Monozygotic twin studies indicate that discordance rate in MG is about 70-60%, suggesting that despite identical DNA unknown factors contribute to disease development. The aim of the current study was to identify novel disease-associated genes in purified monocytes, including both genes associated with predisposition or with disease course, using the unique model of MZ twins. Thus the transcriptome and methylome were compared between twins discordant and concordant for the diseases, as well as MG singletons, and healthy controls. Several transcripts associated with immune homeostasis and inflammation resolution were highlighted in the current study. High similarity between the healthy and the MG discordant twins found, suggest that genetic predisposition may have a stronger contribution then previously assumed. In addition, results suggest that numerous small changes in expression and DNA methylation might contribute to disease onset making it more difficult to pick up
Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins.
Sex, Age, Specimen part
View SamplesPatients with systemic lupus erythematosus (SLE) have a markedly increased risk to develop cardiovascular disease, and traditional cardiovascular risk factors fail to account for this increased risk. We used microarray to probe the platelet transcriptome in individuals with SLE and healthy controls, and the gene and protein expression of a subset of differentially expressed genes was further investigated and correlated to platelet activation status. Real-time PCR was used to confirm a type I interferon (IFN) gene signature in patients with SLE, and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (p<0.0001) were found to be up-regulated in platelets from SLE patients as compared to healthy volunteers. Notably, patients with a history of vascular disease had increased expression of type I IFN-regulated proteins as well as more activated platelets as compared with patients without vascular disease. We suggest that interferogenic immune complexes stimulate production of IFN which up-regulates the megakaryocytic type I IFN-regulated genes and proteins. This could affect platelet activation and contribute to development of vascular disease in SLE. In addition, platelets with type I IFN signature could be a novel marker for vascular disease in SLE.
Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease.
Sex, Age, Specimen part, Disease
View SamplesPediatric high-grade gliomas (pHGGs) harboring the K27M mutation of H3F3A (histone H3.3) are characterized by global reduction of the repressive histone mark H3K27me3 and DNA hypomethylation.
Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas.
Sex, Age, Disease, Disease stage
View SamplesThe importance of the role of microRNAs in gene expression and disease is well recognized. However, what is less appreciated is that almost half of miRNA genes are organized in polycistronic clusters and are therefore co-expressed. The mir-11~998 cluster consists of two miRNAs, miR-11 and miR-998. Here, we describe a novel layer of regulation that links the processing and expression of miR-998 to the presence of the mir-11 gene. We show that the presence of mir-11 in the pri-miRNA is required for processing by Drosha, and deletion of mir-11 prevents the expression of miR-998. Replacing mir-11 with an unrelated miRNA rescued miR-998 expression in vivo and in vitro, as did expressing miR-998 from a shorter, more canonical miRNA scaffold. The embedded regulation of miR-998 is functionally important because unchecked miR-998 expression in the absence of miR-11 resulted in highly penetrant pleiotropic developmental defects. We further show that this novel regulation of expression of miRNAs within a cluster is not limited to the mir-11~998 cluster and likely reflects the more general cis-regulation of expression of individual miRNAs. Thus, our results reveal a novel layer of regulation within miRNA clusters that tempers the functions of the individual miRNAs. Unlinking their expression has the potential to change the expression of multiple miRNA targets and shift biological response. Overall design: RNA was extracted from Drosophila third instar larval eye discs of animals grown in standard conditions; Illumina HiSeq2000 Next Gen RNA Sequencing was performed, and differential expression of genes was assessed in wild-type vs unchecked miR-998 expression
Novel regulation and functional interaction of polycistronic miRNAs.
Specimen part, Subject
View SamplesExpression of dE2F1 induces proliferation and apoptosis. We sought to perform an unbiased analysis of the effect of co-expression of miR-11
mir-11 limits the proapoptotic function of its host gene, dE2f1.
Specimen part
View SamplesThe GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and beta-lactams such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two pump genes most negatively affected by NorG were NorC (4-fold) and AbcA (6-fold). Other categories of genes such as those participating in amino acid, inorganic ion, or nucleotide transporters and metabolism, were also affected by NorG. Real-time RT-PCR assays for mgrA, arlS, sarZ, norB, norC, abcA, mmpL, and bcrA-like were carried out to verify microarray data and showed the same level of up- or down regulation by NorG. The norG mutant showed a twofold increase in the resistance to norfloxacin and rhodamine, both substrates of the NorC transporter, which is consistent with the resistance phenotype conferred by overexpression of norC on a plasmid. These data indicate that NorG has broad regulatory function in S. aureus.
Transcriptional profiling analysis of the global regulator NorG, a GntR-like protein of Staphylococcus aureus.
No sample metadata fields
View SamplesWe implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis.
Probing the Xenopus laevis inner ear transcriptome for biological function.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Otitis media impacts hundreds of mouse middle and inner ear genes.
Age, Specimen part, Treatment
View SamplesObjective: Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition.
Otitis media impacts hundreds of mouse middle and inner ear genes.
Age, Specimen part, Treatment
View Samples