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GSE41171
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development and increased incidences of exencephaly. Moreover, in line with an overlap of Jarid1b and Polycomb targets genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants. Genome-wide analysis demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 in early Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators in knockouts. Taken together, these results suggest that Jarid1b contributes to mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications.
Publication Title
The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 30 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st), Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
CaSR modulation inhibits neuroblastoma growth
Publication Title
Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st), Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
CaSR modulation inhibits neuroblastoma growth
Publication Title
Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 23 Downloadable Samples
- Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
DNA methylation changes in neuroblastoma, a clinically-heterogeneous pediatric tumor, have been described essentially in promoter regions. We analyzed the DNA methylome of neuroblastoma using high-density microarrays and observed differential methylation not only in promoters but also in intragenic and intergenic regions at both CpG and non-CpG sites. These epigenetic changes showed a non-random distribution relative functional chromatin domains, and targeted development and cancer-related genes, relevant for neuroblastoma pathogenesis. CCND1, a gene overexpressed in neuroblastoma, showed hypomethylation of gene-body and upstream regulatory regions. Furthermore, tumors with diverse clinical-risk showed clear differences affecting CpG and, remarkably, non-CpG sites. Non-CpG methylation was present in clinically-favorable tumors and affected genes such as ALK, where non-CpG methylation correlated with low gene expression. Finally, we identified CpG and non-CpG methylation signatures which correlated with patients age at time-points relevant for neuroblastoma clinical behavior, and targeted genes related to neural development and neural crest regulatory network
Publication Title
DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Multispecies miRNA-3 Array (mirna3), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Surgery-Induced Weight Loss Is Associated With the Downregulation of Genes Targeted by MicroRNAs in Adipose Tissue.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st), Affymetrix Multispecies miRNA-3 Array (mirna3)
Description
Molecular mechanisms associated with pathophysiological variations in adipose tissue (AT) are not fully recognized. The main aim of this study was to identify novel candidate genes and miRNAs that may contribute to the pathophysiology of hyperplastic AT. Therefore, wide gene and microRNA (miRNA) expression patterns were assessed in subcutaneous AT of 16 morbidly obese women before and after surgery-induced weight loss. Validation of microarray data was performed by quantitative real-time PCR both longitudinally (n=25 paired samples) and cross-sectionally (25 obese vs. 26 age-matched lean women). Analyses in macrophages and differentiated human adipocytes were also performed to try to comprehend the associations found in AT. 5,018 different probe sets identified significant variations in gene expression after treatment (adjusted p-value<0.05). A set of 16 miRNAs also showed significant modifications. Functional analysis revealed changes in genes and miRNAs associated with cell cycle, development and proliferation, lipid metabolism, and the inflammatory response. Canonical affected pathways included TREM1, PI3K, and EIF2 signaling, hepatic stellate cell activation, and mitochondrial function. Increased expression of SLC27A2, ELOVL6, FASN, GYS2, LGALS12, PKP2, ACLY, and miR-575, as well as decreased FOS, EGFL6, PRG4, AQP9, DUSP1, RGS1, EGR1, SPP1, LYZ, miR-130b, miR-221, and miR-155, were further validated. The clustering of similar expression patterns for gene products with related functions revealed molecular footprints, some of them described for the first time, which elucidate changes in biological processes after the surgery-induced weight loss.
Publication Title
Surgery-Induced Weight Loss Is Associated With the Downregulation of Genes Targeted by MicroRNAs in Adipose Tissue.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Rattus norvegicus
- 5 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Fat metabolism is also peturbed after the diagnosis of type 1 diabetes. Patients have less fat in the liver (4) and increased fasting lipid oxidation (5) compared to controls. Similarly, in a BioBreeding rat model of type 1 diabetes, the diabetes-prone animals develop a reduced respiratory quotient compared to non-diabetic rats before the onset of hyperglycemia, consistent with an increased use of fatty acids relative to carbohydrates as an energy substrate (6).
Publication Title
Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 31 Downloadable Samples
Illumina HiSeq 2500
Description
C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, is primarily expressed on cells of the myeloid lineage, and to a lesser extent on endothelial cells and neurons in brain. Previous work demonstrated C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in Alzheimer Disease (AD) mouse models. In the Arctic AD mouse model, genetic deletion of C5aR1 prevented behavior deficits at 10 months. However, the molecular mechanisms of this protection has not been definitively demonstrated. To understand the role of microglial C5aR1 in the Arctic AD mouse model, we have taken advantage of the CX3CR1GFP and CCR2RFP reporter mice to distinguish microglia as GFP-positive and infiltrating monocytes as GFP and RFP positive, for subsequent transcriptome analysis on specifically sorted myeloid populations from wild type and AD mouse models. Immunohistochemical analysis of mice aged to 2, 5, 7 and 10 months showed no change in amyloid beta (Ab) deposition in the Arctic C5aR1 knockout (KO) mice relative to that seen in the Arctic mice. Of importance, no CCR2+ monocytes/macrophages were found near the plaques in the Arctic brain with or without C5aR1. RNA-seq analysis on microglia from these mice identified inflammation related genes as differentially expressed, with increased expression in the Arctic mice relative to wildtype and decreased expression in the Arctic/C5aR1KO relative to Arctic. In addition, phagosomal-lysosomal proteins and protein degradation pathways that were increased in the Arctic mice were further increased in the Arctic/C5aR1KO mice. These data are consistent with a microglial polarization state with restricted induction of inflammatory genes and enhancement of clearance pathways. Overall design: Microglia mRNA profiles of wildtype (WT), C5aR1 knockout (C5aR1KO), Arctic (ARC) and Arctic C5aR1 knockout (ARCKO) mice at 2, 5, 7 and 10-11 month. Duplicates were sequenced for each genotype on Illumina HiSeq 2500 platform.
Publication Title
Prevention of C5aR1 signaling delays microglial inflammatory polarization, favors clearance pathways and suppresses cognitive loss.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples