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GSE80603
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Endometriosis is a benign gynecological condition that causes significant morbidity due to reduced fertility, pelvic pain and inflammatory dysfunctions. High-fat dietary intake has been linked to higher systemic inflammation and oxidative stress, which are both features of women with endometriosis. We evaluated the effects of high-fat diet (HFD) on endometriosis progression using immunocompetent mouse model wherein ectopic lesion was induced in wildtype and kruppel-like factor 9 (KLF9)- null donor mice. Results showed that HFD leads to increased ectopic lesion numbers and higher body weight gain. The HFD-promotion of lesion establishment was associated with decreased stromal estrogen receptor 1 and progesterone receptor expression, increased macrophage infiltration, and enhanced expression of pro-inflammarory and pro-oxidative stress pathway genes. Further, lesion-bearing mice had higher peritoneal fluid TNF- and elevated local/systemic redox status than control-fed mice.
Publication Title
High-Fat Diet Promotion of Endometriosis in an Immunocompetent Mouse Model is Associated With Altered Peripheral and Ectopic Lesion Redox and Inflammatory Status.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 81 Downloadable Samples
Illumina HiSeq 4000
Description
The ability for cut tissues to join together and form a chimeric organism is a remarkable property of many plants, however, grafting is poorly characterized at the molecular level. To better understand this process we monitored genome-wide temporal and spatial gene expression changes in grafted Arabidopsis thaliana hypocotyls. Tissues above and below the graft rapidly developed an asymmetry such that many genes were more highly expressed on one side than the other. This asymmetry correlated with sugar responsive genes and we observed an accumulation of starch above the graft that decreased along with asymmetry once the sugar-transporting vascular tissues reconnected. Despite the initial starvation response below the graft, many genes associated with vascular formation were rapidly activated in grafted tissues but not in cut and separated tissues indicating that a recognition mechanism activated that was independent of functional vascular connections. Auxin which is transported cell-to-cell, had a rapidly elevated response that was symmetric, suggesting that auxin was perceived by the root within hours of tissue attachment to activate the vascular regeneration process. A subset of genes were expressed only in grafted tissues, indicating that wound healing proceeded via different mechanisms depending on the presence or absence of adjoining tissues. Such a recognition process could have broader relevance for tissue regeneration, inter-tissue communication and tissue fusion events. Overall design: We analyzed the poly-adenylated transcriptomes of Arabidopsis thaliana hypocotyle tissue during grafting. Our dataset contains 82 strand-specific samples, whereas each condition is represented by two biological replicates.
Publication Title
Transcriptome dynamics at <i>Arabidopsis</i> graft junctions reveal an intertissue recognition mechanism that activates vascular regeneration.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
YB-1 controls epithelial-mesenchymal transitions by restricting translation of growth-related mRNAs and enabling expression of EMT-inducing transcription factors. We used microarrays to characterize the direct transcriptional and indirect translational regulation of mRNAs by exogenous YB-1 in breast cancer cell lines.
Publication Title
Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Epidemics of influenza virus are of great challenges to the public concern. The lung inflammation and injury caused by excessive inflammatory cell infiltration into the lungs and overproduction of inflammatory mediators are major consequences during influenza virus infection. Neutrophils are vital for anti-microbial defense. However, the roles of neutrophils during viral infections are less clear. Furthermore, the molecular regulation of neutrophil fate and function at the viral infected sites is largely elusive. We found that BCL6 deficiency in neutrophils, but not in monocytes nor lung macrophages, attenuated host inflammation and morbidity following influenza infection. Mechanistically, BCL6 bound to the neutrophil gene loci involved in cellular apoptosis specifically at the site of infection. As such, BCL6 disruption resulted in increased expression of apoptotic genes in neutrophils in the respiratory tract, but not in the circulation nor bone marrow. Consequently, BCL6 deficiency promoted tissue neutrophil apoptosis. Our results have revealed a previously unappreciated role of BCL6 in modulating neutrophil apoptosis at the site of infection for the regulation of host disease development following viral infection. Overall design: Neutrophils were flow sorted based on their surface expression of CD11b and Ly6G from total lung cells of MRP8-Cre Bcl6 or Bcl6 fl/fl mice at day 6 post influenza virus infection. Total RNA was isolated and RNA-seq was performed.
Publication Title
BCL6 modulates tissue neutrophil survival and exacerbates pulmonary inflammation following influenza virus infection.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 140 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Acute lymphoblastic leukemia (ALL), the commonest childhood malignancy, is characterized by recurring gross and submicroscopic structural genetic alterations that contribute to leukemogenesis. Disordered epigenetic regulation is a hallmark of many tumors, and while analysis of DNA methylation of limited numbers of genes or ALL samples suggests epigenetic alterations may also be important, a large-scale integrative genome-wide analysis evaluating DNA methylation in ALL has not been performed. Here, we report an integrated epigenomic, transcriptional and genetic analysis of 167 childhood ALL cases, comprising B-progenitor ALL with hyperdiploidy (N=26), ETV6-RUNX1 (N=27), TCF3-PBX1 (N=9), BCR-ABL1 (N=19), rearrangement of MLL (MLLr) (N=20), rearrangement of CRLF2 (N=11, CRLF2r), deletion of ERG (N=11), miscellaneous or normal karyotype (N=14), and T-lineage ALL (N=30), including 4 MLLr cases and 7 cases with early T-cell precursor immunophenotype. Genome-wide profiling of structural DNA alterations was performed for all cases using Affymetrix 500K and SNP 6.0 arrays. Affymetrix U133A gene expression profiling data was available for 154 cases. Genome-wide methylation profiling was performed using the HELP microarray assay, which measures methylation at approximately 50,000 CpGs distributed among 22,722 Refseq promoters. Methylation data was compared to that of normal pro-B (CD34+CD19+sIg-), pre-B (CD34-CD19+sIg-) and mature B (CD34-CD19+sIg+) cells FACS-sorted from bone marrow of 6 healthy individuals. Unsupervised hierarchical clustering of the top 4043 most variable methylation probesets identified 9 B-ALL clusters with significant correlation to specific genetic lesions including ETV6-RUNX1, MLLr, BCR-ABL1, CRLF2r, TCF3-PBX1 and ERG deletion. T-ALLs and hyperdiploid B-ALLs also defined specific DNA methylation clusters. Supervised analysis including limma and ANOVA identified distinct DNA methylation signatures for each subtype. Notably, the strength of these signatures was subtype dependent, with more differentially methylated genes observed in ALL cases with genetic alterations targeting transcriptional regulators (e.g. ETV6-RUNX1 and MLLr) and fewer genes in cases with alterations deregulating cytokine receptor signaling (e.g. CRLF2r). Aberrant DNA methylation affected specific and distinct biological processes in the various leukemia subtypes implicating epigenetic regulation of these pathways in the pathogenesis of these different forms of ALL (e.g. TGFB and TNF in ERG deleted leukemias; telomere and centriole regulation in BCR-ABL1 ALL). Aberrantly methylated genes were also enriched for binding sites of known or suspected oncogenic transcription factors that might represent cooperative influences in establishing the phenotype of the various B-ALL subtypes. Most importantly, an integrated analysis of methylation and gene expression of these ALL subtypes demonstrated striking inversely correlated expression of the corresponding gene transcripts. The methylation signatures of each subtype exhibited only partial overlap with those of normal B cells, indicating that the signatures do not simply reflect stage of lymphoid maturation. In a separate approach, we discovered that 81 genes showed consistent aberrant methylation across all ALL subtypes, including the tumor suppressor PDZD2, HOXA5, HOXA6 and MSH2. Inverse correlation with expression was confirmed in 66% of these genes. These data suggest the existence of a common epigenetic pathway underlying the malignant transformation of lymphoid precursor cells. Integrative genetic and epigenetic analysis revealed hypermethylation of genes on trisomic chromosomes that do not show increased expression, suggesting that epigenetic silencing may control genes within amplified regions and explain why only selected genes are overexpressed. Finally, analysis of individual genes targeted by recurring copy number alterations in ALL revealed a subset of genes also targeted by abnormal methylation, with corresponding changes in gene expression (e.g. ERG, GAB1), suggesting that such genes are inactivated far more frequently than suggested by genetic analyses alone. Collectively, the data support a key role of epigenetic gene regulation in the pathogenesis of ALL, and point towards a scenario where genetic and epigenetic lesions cooperatively determine disease phenotype.
Publication Title
Integrated genetic and epigenetic analysis of childhood acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 67 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We performed DNA methylation (HELP array) and gene expression profiling in 69 samples of diffuse large B cell lymphoma (DLBCL). First, by gene expression, two molecular subtypes of DLBCL termed as "germinal center B cell-like" (GCB) and "activated B cell-like" (ABC) DLBCL were assigned to the 69 DLBCL cases. Then, the supervised analysis using HELP data revealed strikingly different DNA promoter methylation patterns in the two molecular DLBCL subtypes. These data provide epigenetic evidence that the DLBCL subtypes are distinct diseases that utilize different oncogenic pathways.
Publication Title
DNA methylation signatures define molecular subtypes of diffuse large B-cell lymphoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The scaffold attachment factors SAFB1 and SAFB2 are paralogs, which are involved in cell cycle regulation, apoptosis, differentiation, and stress response. They have been shown to function as estrogen receptor co-repressors, and there is evidence for a role in breast tumorigenesis. To identify their endogenous target genes in MCF-7 breast cancer cells, we utilized gene expression array analysis, which was set up in a two-by-four design, with vehicle and estrogen treatment, and control, SAFB1, SAFB2, and SAFB1/SAFB2 siRNA as variables. Using custom chips containing 1.5 kb upstream regulatory region, we identified 541 SAFB1/SAFB2 binding sites in promoters of known genes, with significant enrichment on chromosome 1 and 6. Gene expression analysis revealed that the majority of target genes were induced in the absence of SAFB1 or SAFB2, and less were repressed. In contrast to SAFB2, which shared most of its target genes with SAFB1, SAFB1 had many unique target genes, most of them involved in regulation of the immune system. A subsequent analysis of the estrogen treatment group revealed that twelve percent of estrogen-regulated genes were dependent on SAFB1, with the majority being estrogen-repressed genes. These were primarily genes involved in apoptosis, such as BBC3, NEDD9, and OPG. Thus, this study confirms SAFB1/SAFB2s primary role as co-repressors, and also uncovers a previously unknown role for SAFB1 in regulation of immune genes, and in estrogen-mediated repression of genes.
Publication Title
SAFB1 mediates repression of immune regulators and apoptotic genes in breast cancer cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Maternal 5-HT1A-receptor (R) is required for the timely development of the hippocampus and the establishment of emotional behaviors in Swiss-Webster (SW) mice. A partial and/or complete loss of maternal 5-HT1AR results in delayed ventral dentate granule cell (v-DGC) development and subsequent anxiety-like phenotype in the wild-type offspring by a non-genetic, presumably epigenetic mechanism. Here we tested v-DGCs for genome-wide DNA methylation changes elicited by the receptor deficient maternal environment. We identified a set of hypomethylated regions in the offspring of receptor deficient mothers. A significant fraction of these maternal-differentially methylated regions (m-DMRs) mapped to strong CpG islands, sequences that are typically not methylated or if methylated, resistant to environmental-induced changes. Many m-DMRs mapped to exons and some were associated with expression changes. Their hypomethylation was due to an arrest in de novo methylation and, to a lesser extent, to demethylation during postnatal life indicating that the perturbation in methylation coincides with the developmental delay in DGC maturation in the offspring of receptor deficient mothers. Inhibiting methylation in differentiating neurons impaired their maturation further suggesting a link between de novo methylation and neuronal differentiation. These data suggest that methylation at specific exonic CpG-islands may contribute to the mechanism through which maternal 5-HT1AR modulates hippocampal development and consecutively the level of anxiety in the SW offspring. Reduced 5-HT1AR-binding has been reported in individuals, particularly in association with anxiety/depression, including peri/postpartum depression. Therefore, maternal receptor deficit may contribute, via a non-genetic mechanism, to the high prevalence and heritability of anxiety disorders in human. Overall design: Examined transcriptomes of 5HT1A wild type offspring with 5HT1A wild type/heterozygous mother or 5HT1A KO offspring with 5HT1A of heterozygous/knock out mother
Publication Title
Differential gene body methylation and reduced expression of cell adhesion and neurotransmitter receptor genes in adverse maternal environment.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PAR-1 is known to be involved in the transition from non-metastatic to metastatic melanoma. We sought to determine the downstream target genes regulated by PAR-1 to determine how PAR-1 is contributing to the metastatic melanoma phenotype.
Publication Title
Protease activated receptor-1 inhibits the Maspin tumor-suppressor gene to determine the melanoma metastatic phenotype.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Escherichia coli, Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systematic Functional Dissection of Common Genetic Variation Affecting Red Blood Cell Traits.
Sample Metadata Fields
Specimen part, Cell line
View Samples