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SRP011006
Drosophila melanogaster
6 Downloadable Samples
Illumina HiSeq 2000
Description
Dnmt2 genes are highly conserved tRNA methyltransferases with biological roles in cellular stress responses. The absence of obvious mutant phenotypes under laboratory conditions suggested a function for Dnmt2 under non-physiological conditions. Indeed, Dnmt2 has recently been implicated in various aspects of the cellular stress response and the tRNA methyltransferase activity of Dnmt2 has been shown to interfere with stress-induced fragmentation of various tRNAs. We used adult animals and small RNA sequencing during a heat stress experiment to determine the tRNA fragment abundance and identities in wild-type and Dnmt2 mutant somatic tissues. Dnmt2 mutants produced tRNA fragments with different identities when compared to wild-type controls, indicating the accumulation of non-physiological tRNA-derived molecules in tissues without Dnmt2. Overall design: 6 samples examined: heterozygous and Dnmt2 mutant under control, heat shock and recovery conditions
Publication Title
The RNA methyltransferase Dnmt2 is required for efficient Dicer-2-dependent siRNA pathway activity in Drosophila.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 1 Downloadable Sample
- Illumina HiSeq 2000
Description
Dnmt2 genes are highly conserved tRNA methyltransferases with biological roles in cellular stress responses. Dnmt2 has recently been implicated in transposon silencing in Drosophila but the exact molecular mechanisms are unclear. Adult Dnmt2 mutants were heat shocked and RNA sequencing was performed on visible high-molecular weight RNAs to determine the identity of up-regulated transposons. Dnmt2 mutants accumulated almost all families of transposons after heat shock, indicating a general mis-regulation of transposon silencing in Dnmt2 mutants during the stress response. Overall design: one sample, excised, electroeluted and pooled RNA of different molecular weight, Dnmt2 mutant during recovery from a single heat shock
Publication Title
Mutations in Cytosine-5 tRNA Methyltransferases Impact Mobile Element Expression and Genome Stability at Specific DNA Repeats.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
This study uses whole-transcriptome sequencing to characterize the transcriptomes of the AOM/DSS mouse model. In this model, mice are treated with dextran sodium sulfate (DSS) to induce colitis. When this treatment is preceded by injections of the weak carcinogen azoxymethane (AOM) the mice develop intestinal tumors. Our results identify sets of differentially expressed genes which are correlated with methylation changes of the corresponding genes. Overall design: Whole transcriptome analysis of Mus musculus. Three conditions were sequenced and analyzed, the first is an untreated control, the second corresponds to inflammation induced by applying DSS, the third to cancer induced by inflammation and application of AOM. The control condition as well as the AOM-induced cancer condition were analyzed using three replicates, the second condition using 4 replicates.
Publication Title
Chronic inflammation induces a novel epigenetic program that is conserved in intestinal adenomas and in colorectal cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Stem and progenitor cells maintain the tissue they reside in for life by regulating the balance between proliferation and differentiation. How this is done is not well understood. Here, we report that DDX6 is necessary for maintaining human epidermal progenitor cell self-renewal.
Publication Title
DDX6 Orchestrates Mammalian Progenitor Function through the mRNA Degradation and Translation Pathways.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
miR-17 from the miR-17-92 cluster regulate activation-induced cell death in T cells and modulate inducible regulatory T cell differentiation.
Publication Title
Molecular dissection of the miR-17-92 cluster's critical dual roles in promoting Th1 responses and preventing inducible Treg differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer remains a major clinical problem. Recently, the CDK4/6 inhibitor palbociclib combined with letrozole was approved for treatment of ER+ advanced breast cancer, and other CDK4/6 inhibitors are being investigated in combination with different endocrine treatments. However, the role of CDK4/6 in endocrine resistance and their potential as predictive biomarkers of endocrine treatment response remains undefined.
Publication Title
High CDK6 Protects Cells from Fulvestrant-Mediated Apoptosis and is a Predictor of Resistance to Fulvestrant in Estrogen Receptor-Positive Metastatic Breast Cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To elucidate the molecular mechanisms of tamoxifen resistance in breast cancer, we performed gene array analysis and identified 366 genes with altered expression in four unique tamoxifen resistant (TamR) cell lines vs the parental tamoxifen sensitive MCF7/S0.5 cell line. Most of these genes were funcationally linked to cell proliferation, death and control gene expression, and include FYN, PRKCA, ITPR1, DPYD, DACH1, LYN, GBP1 and PRLR. Treatment with FYN specific small interfering RNA or a SRC family kinase inhibitor reduced cell growth of TamR cell lines while exerting no significant effect on MCF7/S0.5 cells. Moreover, overexpression of FYN in parental tamoxifen-sensitive MCF7/S0.5 cells resulted in reduced sensitivity to tamoxifen, demonstrating growth and survival promoting function of FYN in MCF7 cells. FYN knockdown in TamR cells led to reduced phosphorylation of 14-3-3 and CDc 25A, suggesting that FYN, by activation of of important cell cycle-associated proteins, may overcome the anti-proliferative effects of tamoxifen. Evaluation of the subcellular localization of FYN in primary breast tumors from two cohorts of endocrine-treated ER+ breast cancer patients, one with advanced disease (N = 47) and the other with early disease (N = 76), showed that in the former, plasma membrane-associated FYN expression strongly correlated with longer progression-free survival (P<0.0002). Similarly, in early breast cancer patients, membrane-associated expression of FYN in the primary breast tumor was significantly associated with increased metastasis-free (P<0.04) and overall (P<0.004) survival independent of tumor size, grade or lymph node status. Our results indicate that FYN has an important role in tamoxifen resistance, and its subcellular localization in breast tumor cells may be an important novel biomarker of response to endocrine therapy in breast cancer.
Publication Title
Gene expression profiling identifies FYN as an important molecule in tamoxifen resistance and a predictor of early recurrence in patients treated with endocrine therapy.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Sus scrofa
- 16 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Caesarean-delivered preterm pigs were fed 3 d of parenteral nutrition followed by 2 d of enteral formula feeding. Antibiotics (n=11) or control saline (n=13) were given twice daily from birth to tissue collection at d 5. NEC-lesions and intestinal structure, function, microbiology and immunity markers were recorded.
Publication Title
Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
Description
Purpose: Development of resistance to tamoxifen is an important clinical issue in the treatment of patients with breast cancer. Tamoxifen resistance may be the result of the acquisition of epigenetic regulation such as DNA methylation within breast cancer cells resulting in changed mRNA expression of genes being pivotal for estrogen dependent growth. Alternatively, tamoxifen resistance may be due to selection of preexisting resistant cells, which may exhibit cancer stem-like characteristics or a combination of the two mechanisms. Methods: To evaluate the contribution of these possible mechanisms to tamoxifen resistance, we applied modified DNA methylation-specific digital karyotyping (MMSDK) and digital gene expression (DGE) in combination with massively parallel sequencing to analyze a well-established tamoxifen resistant cell line model: MCF-7/S0.5 (tamoxifen sensitive parental cell line) and 4 high-dosage tamoxifen selected resistant offspring sublines (MCF-7/TAMR-1, MCF-7/TAMR-4, MCF-7/TAMR-7 and MCF-7/TAMR-8). MMSDK uses BssHII as mapping enzyme (DNA methylation sensitive enzyme). Both MMSDK and DGE use NlaIII and MmeI to produce 20-21 bp tag. The indexed single-end sequencing was performed by Illumina HiSeq 2000 in BGI-Shenzhen. A dynamic programming algorithm-FASTX-Toolkit implemented in Perl was used to trim the adaptor sequence. The trimmed tags were subjected to quality filtering, so that only tags with sequencing quality higher than 30 for more than 80% of the nucleotides were used for subsequent analysis. For MMSDK tag mapping, we generated a simulated reference library, i.e., BssHII reference library, by in silico enzyme digestion of the human genome (hg19, UCSC) regardless of the methylation state. This library was used as reference for subsequent mapping of the tags in the MMSDK analysis. In the DGE analysis, refMrna (hg19, UCSC) was used as reference for mapping cDNA tags. Subsequently, the Burrows–Wheeler Aligner (BWA) procedure for aligning the MMSDK and DGE tags to the simulated BssHII reference library and refMrna reference library, respectively, was applied. Results: MMSDK libraries using BssHII/NlaIII were generated from the parental tamoxifen sensitive subline MCF-7/S0.5 and the 4 TAMR cell lines: TAMR-1, TAMR-4, TAMR-7 and TAMR-8. The 5 indexed MMSDK libraries were sequenced in one lane and 1.38 Gb clean tag data for all 5 cell lines were obtained, with an average sequencing amount of ~270 Mb per library. On average, 59.5 % of the tags with mapping quality = 20 were mapped back to the simulated BssHII/NlaIII reference library. DGE libraries were also generated from MCF-7/S0.5 and the 4 TAMR cell lines. The 5 indexed DGE libraries were sequenced in one lane and obtained 1.71 Gb clean tag data for all 5 cell lines with an average sequencing amount of ~340 Mb per library. On average, 40.8 % with mapping quality = 20 were mapped back to the simulated NlaIII human transcriptome (refMrna reference library). Our present study demonstrates large differences in global gene expression and DNA methylation profiles between parental tamoxifen-sensitive cell line and 4 high-dosage tamoxifen treatment selected resistant sublines. The tamoxifen resistant cell lines exhibited globally higher methylation level than the parental cell line and an inverse relationship between gene expression and DNA methylation in the promoter regions were noticed. High expression of SOX2 and alterations of other SOX gene family members, E2F gene family members and RB-related pocket protein genes as well as highlighted stem cell pathways imply that cancer initiating cells/stem cells are involved in the resistance to tamoxifen. Overall design: DNA methylation and mRNA expression profiles from tamoxifen sensitive parental cell line MCF-7/S0.5 and 4 high dosage of tamoxifen selected resistant offspring sublines (MCF-7/TAMR-1, MCF-7/TAMR-4, MCF-7/TAMR-7 and MCF-7/TAMR-8) were analyzed by MMSDK and DGE methods, respectively, in combination of massively parallel sequencing, using Illumina HiSeq 2000
Publication Title
Integrative analyses of gene expression and DNA methylation profiles in breast cancer cell line models of tamoxifen-resistance indicate a potential role of cells with stem-like properties.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 63 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.
Sample Metadata Fields
Age, Specimen part, Disease, Cell line, Treatment
View Samples