Filters
Technology
Platform
GSE89079
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We report that Zic family (Zic1/2/3) and orphan nuclear receptors family (Esrrb and Nr5a2) transcription factors (TFs) synergistically enhance the reprogramming efficiency when transduced with Oct4, Sox2 and Klf4 (OSK) into murine fibroblasts. To identify the molecular mechanisms underlying this synergy, we analyzed global gene expression at 6 days after introduction of reprogramming factors. As a result, we found that primary targets of these TFs are different when either of TFs was introduced with OSK, but a significant portion of genes including pluripotency makers such as Dppa2 was synergistically upregulated. Further analysis revealed that metabolic pathways are the important targets of these TFs for efficient reprogramming.
Publication Title
Hybrid Cellular Metabolism Coordinated by Zic3 and Esrrb Synergistically Enhances Induction of Naive Pluripotency.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
In C. elegans, ablation of germline stem cells (GSCs) extends lifespan, but also increases fat accumulation and alters lipid metabolism, raising the intriguing question of how these effects might be related. Here we show that a lack of GSCs results in a broad transcriptional reprogramming, in which the conserved detoxification regulator SKN-1/Nrf increases stress resistance, proteasome activity, and longevity. SKN-1 also activates diverse lipid metabolism genes and reduces fat storage, thereby alleviating the increased fat accumulation caused by GSC absence. Surprisingly, SKN-1 is activated by signals from this fat, which appears to derive from unconsumed yolk that was produced for reproduction. We conclude that SKN-1 plays a direct role in maintaining lipid homeostasis, in which it is activated by lipids. This SKN-1 function may explain the importance of mammalian Nrf proteins in fatty liver disease, and suggests that particular endogenous or dietary lipids might promote health through SKN-1/Nrf. Overall design: Samples were prepared from ~5,000 synchronized, L1 arrested day-one adult animals cultured at 25°C. Worms were synchronized by sodium hypochlorite (bleach) treatment, as previously described (Porta-de-la-Riva et al., 2012). Bleach solution (9 mL ddH2O; 1 mL 1 N NaOH; 4 mL Clorox bleach) was freshly prepared before each experiment. Worms were bleached for 5 minutes, washed 5x in M9, and arrested at the L1 stage at 25°C in M9 containing 10 µg/mL cholesterol. Feeding RNAi was started at the L1 stage. This approach only partially reduces skn-1 function, but allows analysis of larger samples than would be feasible with skn-1 mutants, which are sterile (Bowerman et al., 1992). Because these animals were not treated with FUdR, the WT adults contained an intact germline and eggs. As is explained in the Results section, we therefore confined our analysis to genes that were overrepresented in glp-1(ts) animals, which lack eggs and most of the germline, and established a high-confidence cutoff for genes that were upregulated by GSC absence as opposed to simply being expressed specifically in somatic tissues. RNA was extracted using the same protocol for qRT-PCR samples. Purified RNA samples were DNase treated and assigned a RIN quality score using a Bioanalyzer 2100 (Agilent Technologies, Santa Clara, CA). Only matched samples with high RIN scores were sent for sequencing. Single read 50 bp RNA sequencing with poly(A) enrichment was performed at the Dana-Farber Cancer Institute Center for Computational Biology using a HiSeq 2000 (Illumina, San Diego, CA). FASTQ output files were aligned to the WBcel235 (Feb 2014) C. elegans reference genome using STAR (Dobin et al., 2013). These files have been deposited at the Gene Expression Omnibus (GEO) with the accession number GSE63075. Samples averaged 75% mapping of sequence reads to the reference genome. Differential expression analysis was performed using a custom R and Bioconductor RNA-seq pipeline (http://bioinf.wehi.edu.au/RNAseqCaseStudy/) (Gentleman et al., 2004; Anders et al., 2013; R Core Team, 2014). Quantification of mapped reads in the aligned SAM output files was performed using featureCounts, part of the Subread package (Liao et al., 2013, 2014). We filtered out transcripts that didn't have at least one count per million reads in at least two samples. Quantile normalization and estimation of the mean-variance relationship of the log-counts was performed by voom (Law et al., 2014). Linear model fitting, empirical Bayes analysis and differential expression analysis was then conducted using limma (Smyth, 2005). To identify genes that are upregulated in a SKN-1-dependent manner by GSC loss, we sought genes for which glp-1(ts) expression was higher than WT, and for which glp-1(ts);skn-1(-) expression was reduced relative to glp-1(ts). To test for this pattern, if a gene's expression change was higher in the comparison of glp-1(ts) vs. WT and lower in the comparison of glp-1(ts);skn-1(-) vs. glp-1(ts), then we calculated the minimum (in absolute value) of the t-statistics from these two comparisons, and assessed the significance of this statistic by comparing to a null distribution derived by applying this procedure to randomly generated t-statistics. We corrected for multiple testing in this and the differential expression analysis using the false discovery rate (FDR) (Benjamini and Hochberg, 1995). Heatmaps were generated using heatmap.2 in the gplots package (Warnes et al., 2014). Functional annotations and phenotypes were obtained from Wormbase build WS246. SKN-1 transcription factor binding site analysis of hits was conducted with biomaRt, GenomicFeatures, JASPAR, MotifDb, motifStack, MotIV, and Rsamtools (Sandelin et al., 2004; Durinck et al., 2005; Durinck et al., 2009; Lawrence et al., 2013; Ou et al., 2013; Mercier and Gottardo, 2014; Shannon, 2014). JASPAR analysis was performed with the SKN-1 matrix MA0547.1 using 2 kb upstream sequences obtained from Ensembl WBcel235 (Staab et al., 2013). modENCODE SKN-1::GFP ChIP-seq analysis of hits was performed using biomaRt, ChIPpeakAnno, IRanges, and multtest (Durinck et al., 2005; Durinck et al., 2009; Gerstein et al., 2010; Zhu et al., 2010; Niu et al., 2011; Lawrence et al., 2013). SKN-1::GFP ChIP-seq peaks were generated by Michael Snyder's lab. We used the peak data generated from the first 3 larval stages: L1 (modENCODE_2622; GSE25810), L2 (modENCODE_3369), and L3 (modENCODE_3838; GSE48710). Human ortholog matching was performed using Wormbase, Ensembl, and OrthoList (Shaye and Greenwald, 2011). Gene lists were evaluated for functional classification and statistical overrepresentation with Database for Annotation, Visualization and Integrated Discovery (DAVID) version 6.7 (Dennis et al., 2003).
Publication Title
Lipid-mediated regulation of SKN-1/Nrf in response to germ cell absence.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human pluripotent stem cells (hPSCs) such as embryonic stem cells and induced pluripotent stem cells are promising materials for cell-based regenerative therapies to heart diseases. However, until realization there are many hurdles such as high efficiency of cardiac differentiation of hPSCs and production of clinical-grade cardiac cells derived from hPSCs. Here, we show that a novel small molecule KY02111 robustly enhances differentiation to functional cardiomyocytes from hPSCs.
Publication Title
A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Expression data from Caenorhabditis elegans let-418(RNAi), mep-1(RNAi) and gfp(RNAi) L1 larvae.
Publication Title
Different Mi-2 complexes for various developmental functions in Caenorhabditis elegans.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2500
Description
Hepatic iron overload is a risk factor for progression of hepatocellular carcinoma (HCC), although the molecular mechanisms underlying this association have remained unclear. We now show that the iron-sensing ubiquitin ligase FBXL5 is previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatocellular iron overload evoked by FBXL5 ablation gives rise to oxidative stress, tissue damage, inflammation and compensatory proliferation in hepatocytes and to consequent promotion of liver carcinogenesis induced by exposure to a chemical carcinogen. The tumor-promoting effect of FBXL5 deficiency in the liver is also operative in a model of virus-induced HCC. FBXL5-deficient mice thus constitute the first genetically engineered mouse model of liver carcinogenesis induced by iron overload. Dysregulation of FBXL5-mediated cellular iron homeostasis was also found to be associated with poor prognosis in human HCC, implicating FBXL5 plays a significant role in defense against hepatocarcinogenesis. Overall design: Total RNA was extracted from the nontumor and tumor tissue of an Alb-Cre/Fbxl5F/F male mouse (nontumor, n = 5; tumor, n = 5) or two littermate control Fbxl5F/F mice (nontumor, n = 6; tumor, n = 6) at 45 weeks of age.
Publication Title
Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Spaceflight results in a number of adaptations to skeletal muscle, including atrophy and shifts towards faster muscle fiber types. To identify changes in gene expression that may underlie these adaptations, microarray expression analysis was performed on gastrocnemius from mice flown on the STS-108 shuttle flight (11 days, 19 hours) versus mice maintained on earth for the same period. Additionally, to identify changes that were due to unloading and reloading, microarray analyses were conducted on calf muscle from ground-based mice subjected to hindlimb suspension (12 days) and mice subjected to hindlimb suspension plus a brief period of reloading (3.5 hours) to simulate the time between landing and sacrifice of the spaceflight mice.
Publication Title
Effects of spaceflight on murine skeletal muscle gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 1500
Description
Innate immune cells control acute eosinophilic lung inflammation induced by cystein proteases. Here we characterize the dynamic change of gene expression profile in basophils, natural helper cells and eosinophils during lung inflammation via cystein protease Overall design: Examination of mRNA levels in individual cell populations, basophils, natural helper cells and eosinophils of the lung from naïve mice and papain treated mice.
Publication Title
Basophil-derived interleukin-4 controls the function of natural helper cells, a member of ILC2s, in lung inflammation.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 22 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The development of trichomes (leaf hairs) from pluripotent epidermal cells in Arabidopsis provides a powerful system to investigate the regulatory motifs involved in plant cell differentiation. Genetic studies have revealed that a bHLH transcription factor, GL3, activates downstream genes required for trichome initiation by interacting with a R2R3-MYB protein, GL1. In order to investigate genome-wide regulatory functions of GL1 and GL3, we performed genome-wide expression analyses using GR inducible systems of GL1 and GL3.
Publication Title
A systems approach reveals regulatory circuitry for Arabidopsis trichome initiation by the GL3 and GL1 selectors.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The development of trichomes (leaf hairs) from pluripotent epidermal cells in Arabidopsis provides a powerful system to investigate the regulatory motifs involved in plant cell differentiation. Genetic studies have revealed that a bHLH transcription factor, GL3, activates downstream genes required for trichome initiation by interacting with a R2R3-MYB protein, GL1. We have taken advantage of several mutants in the trichome developmental pathway and gene expression analyses to identify a set of genes expressed predominantly in Arabidopsis trichomes.
Publication Title
A systems approach reveals regulatory circuitry for Arabidopsis trichome initiation by the GL3 and GL1 selectors.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 24 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Alcoholism is a complex disorder determined by interactions between genetic and environmental risk factors. Drosophila represents a powerful model system to dissect the genetic architecture of alcohol sensitivity, as large numbers of flies can readily be reared in defined genetic backgrounds and under controlled environmental conditions. Furthermore, flies exposed to ethanol undergo physiological and behavioral changes that resemble human alcohol intoxication, including loss of postural control, sedation, and development of tolerance.
Publication Title
Phenotypic and transcriptional response to selection for alcohol sensitivity in Drosophila melanogaster.
Sample Metadata Fields
No sample metadata fields
View Samples