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GSE64500
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Unraveling the mechanisms underlying early neural differentiation of ESCs is crucial to the cell-based therapies of neurodegenerate diseases. Neural fate acquisition is proposed to be controlled by a default mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of embryonic stem cells (ESCs). Unexpectedly we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23-depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of other Mediator subunit, Med1 or Med15, did not alter the neural differentiation of ESCs; and Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23-depletion attenuated the BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1 that is involved in the Bmp4 promoter-enhancer communication. Interestingly, Med23 knockdown in zebrafish embryos also enhanced the neural development at early embryogenesis, which could be reversible by coinjection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination.
Publication Title
Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 3 Downloadable Samples
Illumina HiSeq 4000
Description
DNA methylation on N6-adenine (6mA) has recently been found as a potentially new epigenetic mark in several unicellular and multicellular eukaryotes. However, its distribution patterns and potential functions in land plants, which are primary producers for most ecosystems, remain completely unknown. Here we report global profiling of 6mA sites at single-nucleotide resolution in the genome of Arabidopsis thaliana using single-molecule real-time sequencing. 6mA sites are widely distributed across the Arabidopsis genome and enriched over the pericentromeric heterochromatin regions. Nearly 30% of 6mA sites are present in gene bodies. Further analysis of 6mA methylome and RNA-sequencing data demonstrates that 6mA frequency positively correlates with the gene expression level in Arabidopsis. Consistently, histone variants associated with actively expressed genes interact with 6mA DNA. Our results uncover 6mA as a DNA mark associated with actively expressed genes in Arabidopsis, suggesting that 6mA serves as a novel epigenetic mark in land plants. Overall design: RNA-seq in 3-week-old Arabidopsis thaliana (Col-0) wild-type with three replicates.
Publication Title
DNA N<sup>6</sup>-Adenine Methylation in Arabidopsis thaliana.
Sample Metadata Fields
Subject
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Illumina HiScanSQ
Description
Introduction: Though heavy alcohol drinking has been well characterized as causing a variety of injuries, recent epidemiological evidence in humans suggests moderate consumption may provide beneficial effects. For example, there exists a J- or U-shaped relationship between the level of alcohol intake and cardiovascular disease risk. We investigated the underlying mechanisms of these positive consequences by identifying which genes are responsive to moderate alcohol intake in the liver, the primary site for alcohol metabolism. Methods: Twelve female, inbred, alcohol-preferring (iP10a) rats were split equally between chronic water exposure and voluntary chronic ethanol exposure. Hepatic cholesterol and triglyceride levels were analyzed both histologically and biochemically. Hepatic transcriptomes were paired-end sequenced on the Illumina HiScanSQ system. Reads were analyzed and mapped using CLCbio Genomics Workbench 4.9. We confirmed altered expression of a subset of genes using TaqMan-based qRT-PCR. To quantify DNA methylation, we first digested DNA with methylation sensitive restriction enzymes and then performed qPCR using TaqMan assays surrounding the digest sites. Calculating ?Ct between a mock digest and digest determines the percent methylation in that locus. Results: Voluntary alcohol consumption in iP10a rats modeled moderate consumption in humans. These levels did not result in intrahepatic fat accumulation. Sequencing produced ~1.2 Gb of sequence per sample, and 65% of reads mapped uniquely. Using a FDR corrected p value of 0.05 we found 250 altered transcripts. Ontology analysis of genes with a fold change =1.3 identified many cholesterol synthesis genes and cytoskeleton subunit genes, all of which were down-regulated. Of the 28 genes reanalyzed by qRT-PCR, altered expression was confirmed in 24 genes including the majority of the cholesterol synthesis and cytoskeleton subunit genes. Lastly, we profiled methylation throughout the promoter and gene body of four genes elicited in the RNA-Seq experiment. We found that alcohol caused demethylation at all loci; however this loss happened in a site-specific, tightly regulated manner. Conclusion: Voluntary consumption in the iP10a animals models moderate consumption in humans, does not produce intrahepatic fat accumulation, and causes down-regulation of a majority of cholesterol synthesis genes. Moderate alcohol also results in a tightly-regulated demethylation effect. Our results explain, at least in part, the J- or U-shaped relationship between level of alcohol intake and cardiovascular disease risk. Overall design: We sequenced 12 female iP10a rat hepatic transcriptomes providing 6 biological replicates for water control and 6 for ethanol treatment.
Publication Title
A snapshot of the hepatic transcriptome: ad libitum alcohol intake suppresses expression of cholesterol synthesis genes in alcohol-preferring (P) rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Fbw7 plays a negative role in pancreatic cancer tumorigenesis and progression. To further clarify the function and mechanism that Fbw7 plays in pancreatic cancer,mRNA microarray assays were performed to identify the genes and signaling pathways that were changed upon Fbw7 overexpression.
Publication Title
FBW7 (F-box and WD Repeat Domain-Containing 7) Negatively Regulates Glucose Metabolism by Targeting the c-Myc/TXNIP (Thioredoxin-Binding Protein) Axis in Pancreatic Cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 31 Downloadable Samples
- Illumina HiSeq 2000
Description
Exosomes, endosome-derived membrane microvesicles, contain a specific set of RNA transcripts that are involved in cell-cell communication and hold a great potential as disease biomarkers. To systemically characterize exosomal RNA profiles, we performed RNA sequencing analysis using three human plasma samples and evaluated efficacies of small RNA library preparation protocols from 3 manufacturers. Overall design: We tested the six samples (A1 and A2, B1 and B2, C1 and C2) using two small RNA library preparation kits: NEBNext Multiplex Small RNA library Prep Set from New England Biolab (NEB) and NEXTflex Small RNA Sequencing Kit from Bioo Scientific (BS). We also tested Illumina’s TrueSeq Small RNA Sample Preparation Kit (ILMN) in sample A1 and A2. Together, we tested these plasma samples by sequencing 14 indexed libraries. This study allowed direct comparison of current small RNA library preparation protocols and identified the most suitable strategy for future exosomal RNA sequencing analysis.
Publication Title
Characterization of human plasma-derived exosomal RNAs by deep sequencing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We identified microRNA-188 differentially expressed in the BMSCs of aged and young mice and influenced on BMSCs differentiation with ageing.
Publication Title
MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We identified microRNA-188 differentially expressed in the BMSCs of aged and young mice and influented on BMSCs differentiation with ageing.
Publication Title
MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Cells respond to environmental signals by alteration of gene expression through action of transcription factors. A JmjC-domain-containing protein Rph1 belongs to the C2H2 zinc finger protein family and functions to repress transcription of PHR1 via histone demethylation. However, additional targets of Rph1 remain largely unknown. Here, we investigate the regulatory network of Rph1 by microarray analyses. More than 75% of Rph1-regulated genes showed increased expression in rph1, suggesting Rph1 serves as a transcriptional repressor under physiological conditions. The binding motif of Rph1 resembling the STress Response Element (STRE) was over-represented in the promoters of Rph1-repressed genes. In addition, significant proportions of Rph1-regulated genes responded to DNA damage and environmental stress, implying a repressive role of Rph1 in the cross-protection of stress responses.
Publication Title
Dissociation of the H3K36 demethylase Rph1 from chromatin mediates derepression of environmental stress-response genes under genotoxic stress in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 29 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
The innate immune response is primarily mediated by the Toll-like receptors functioning through the Myd88-dependent and TRIF-dependent pathways. Despite being widely studied, it is not yet completely understood and systems-level analyses have been lacking. In this study, we identified a high-probability network of genes activated during the innate immune response using a novel approach to analyze time course gene expression profiles of activated immune cells in combination with a large gene regulatory and protein-protein interaction network. We classified the immune response into three consecutive time-dependent stages and identified the most probable paths between genes showing a significant change in expression at each stage. The resultant network contained several novel and known regulators of the innate immune response, many of which did not show any observable change in expression at the sampled time points. The response network shows the dominance of genes from specific functional classes during different stages of the immune response. It also suggests a role for the protein phosphatase 2a catalytic subunit a in the regulation of the immunoproteasome during the late phase of the response. In order to clarify the differences between the Myd88-dependent and TRIF-dependent pathways in the innate immune response, time course gene expression profiles from Myd88-knockout and TRIF-knockout dendritic cells were analyzed. Their response networks suggest the dominance of the MyD88 dependent pathway in the innate immune response, and an association of the circadian regulators and immunoproteasomal degradation with the TRIF-dependent pathway. The response network presented here provides the most probable associations between genes expressed in the early and the late phases of the immune response, while taking into account the intermediate regulators. We propose that the method described here can also be used in the identification of time-dependent gene subnetworks in other biological systems.
Publication Title
Discovery of Intermediary Genes between Pathways Using Sparse Regression.
Sample Metadata Fields
No sample metadata fields
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