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GSE45859
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In an attempt to elucidate the molecular mechanisms underlying the multiple roles of L1 in endothelium, we checked whether manipulating its expression affected the transcriptome of lECs. To this purpose, we compared the gene expression profiles of L1-overexpressing and control lECs by Affymetrix, which revealed a remarkable effect of L1 overexpression on lECs transcriptome.
Publication Title
Endothelial deficiency of L1 reduces tumor angiogenesis and promotes vessel normalization.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
IlluminaHiSeq2000
Description
In this study we isolated and cultured neural progenitor cells (NPCs) from human fetal brain collected during the gliogenic phase (second trimester) of aborted fetuses, we differentiated NPCs into astrocyte using different protocols (FBS or CNTF/BMP4) and utilized RNA sequencing to analyze transcriptomic changes underlying the differentiation process Overall design: Neural progenitor cells (NPCs) isolated from 4 different donors (91, 103, 110 and 114 days embryos) were differentiated for 1 week using 2.5% FBS, while 3 NPCs lines (two from 103 and one from 110 days embryo) were differentiated for 1 week in the presence of CNTF/BMP4. RNA was extracted from NPCs before and after differentiation and submitted for sequencing on the Illumina HiSeq 2000 platform
Publication Title
A comparative transcriptomic analysis of astrocytes differentiation from human neural progenitor cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To investigate the time-dependent and coordinated sequence of inflammation-related events, and the dynamic features of macrophage polarisation/activation, we build and validated an in vitro model based on primary human monocytes
Publication Title
Transcriptomic profiling of the development of the inflammatory response in human monocytes in vitro.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
These data include RNA Seq data generated from Ring1b wild type and Ring1b KO Ring1a-/- Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa. Overall design: Total RNA extracted from Ring1b wild type and Ring1b KO Ring1a-/- Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa.
Publication Title
Maintenance of leukemic cell identity by the activity of the Polycomb complex PRC1 in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer II
Description
These data include RNA Seq data generated from wild type and Ring1a Ring1b dKO Cdkn2a-/- MLL-AF9 Leukemic cells Overall design: mRNA library preparation from Ring1a-/-;Ring1bf/f Cdkn2a-/- MLL-AF9 leukemic cells treated with OHT or EtOH
Publication Title
Maintenance of leukemic cell identity by the activity of the Polycomb complex PRC1 in mice.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pathways that govern normal stem cell (SC) function are often subverted in cancer. Here, we report the isolation to near purity of human normal mammary SC (hNMSCs), from cultured mammospheres, based on their ability to retain the lipophilic dye PKH26 as a consequence of their quiescent nature. We demonstrated that PKH26-positive cells possess all the characteristics of hNMSCs. The transcriptional profile of PKH26-positive cells (hNMSC signature) was able to predict biological and molecular features of breast cancers. By using markers of the hNMSC signature, we could prospectively isolate SCs from the normal gland and from breast tumors. Poorly-differentiated aggressive (G3) cancers displayed higher content of prospectively isolated cancer SCs, than well-differentiated less aggressive (G1) cancers. By comparing G3 and G1 tumors in xenotransplantation experiments, we directly demonstrated that G3s are enriched in cancer SCs. Our data support the notion that the heterogeneous phenotypical and molecular traits of human breast cancers are a function of their SC content.
Publication Title
Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 94 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
hTERT/cdk4 immortalized myogenic human cell lines represent an important tool for skeletal muscle research, being used as therapeutically-pertinent models of various neuromuscular disorders and in numerous fundamental studies of muscle cell function. However, the cell cycle is linked to other cellular processes such as integrin regulation, the PI3K/Akt pathway, and microtubule stability, raising the question as to whether transgenic modification of the cell cycle results in secondary effects that could undermine the validity of these cell models. Here we subjected healthy and disease lines to intensive transcriptomic analysis, comparing immortalized lines with their parent primary populations in both differentiated and undifferentiated states, and testing their myogenic character by comparison with non-myogenic (CD56-negative) cells. We found that immortalization has no measurable effect on the myogenic cascade or on any other cellular processes, and that it was protective against the systems level effects of senescence that are observed at higher division counts of primary cells.
Publication Title
Skeletal muscle characteristics are preserved in hTERT/cdk4 human myogenic cell lines.
Sample Metadata Fields
Specimen part, Disease, Disease stage
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- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We recently described TRIM8, a nuclear E3 ubiquitin ligase, whose expression inversely correlates with glioma grade. TRIM8 restoration suppresses cell growth and induces a significant reduction of clonogenic potential in both U87MG glioblastoma and patients' primary glioma cell lines. Since E3 ubiquitin ligase proteins regulate carcinogenesis through the timely control of many cellular processes such as DNA damage response, metabolism, transcription, and apoptosis, we reasoned that TRIM8 activity might impact on cell transcriptome patterns, thereby promoting cancer development and progression. Therefore, we profiled the whole transcriptome of normal embryonic neural stem cells (eNSC) infected with a retrovirus expressing FLAG-Trim8 by using RNA-Seq. RNA-Seq revealed 1365 differentially expressed transcripts of 912 genes. 723 of them (corresponding to 648 RefSeq genes) differed significantly of at least 1.5 folds (192 upregulated transcripts of 178 genes and 531 downregulated transcripts of 470 genes). 80 genes, among all differentially expressed genes, resulted to significantly enrich 18 pathways by IPA analysis. 53% of these genes (43 out of 80 genes) are related to cell-morphology, cell death and survival, with a preponderantly representation of signaling pathways related to neurotransmission and to CNS, including axonal guidance, GABA Receptor, ephrin B, synaptic long-term potentiation/depression, and glutamate receptor. Specifically, our results substantiate the role of TRIM8 in the brain functions through the dysregulation of genes involved in different pathways, including JAK-STAT. Finally, we provided additional evidence about the existence of a functional interactive crosstalk between TRIM8 and STAT3 with possible implications in the development and progression of glioma. Overall design: Profiling the transcriptome of TRIM8-expressing primary mouse embryonal neural stem cells using RNA-Seq
Publication Title
TRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Junction Adhesion Molecule-A (JAM-A) is present on leukocytes and platelets where it promotes cell adhesion and motility. We are interested in an interaction between JAM-A and tumor progression/metastases. To address this point, we mated JAM-A-/- mice and mouse mammary tumor model MMTV-PyMT mice which, which express polyoma middle T antigen under the control of mouse mammary tumor virus. MMTV-PyMT mice show 100% penetration of mammary tumor and highly metastases to lung. MMTV-PyMT mice without JAM-A show less primary tumor progression, therefore JAM-A enhance primary tumor progression. Then we are addressing the molecular mechanism of this phenomenon by in vivo. Furthermore, we would like to examine JAM-A deficient MMTV tumor signature.
Publication Title
Abrogation of junctional adhesion molecule-A expression induces cell apoptosis and reduces breast cancer progression.
Sample Metadata Fields
Specimen part
View Samples