Filters
Technology
Platform
GSE119634
Rattus norvegicus
8 Downloadable Samples
Affymetrix Rat Clariom S Assay (clariomsrat)
Description
The study evaluates potential protective effects of cerium oxide nanoparticles (nanoceria) against oxidative stress in muscle tissue, both on ground and in space
Publication Title
Modulation of gene expression in rat muscle cells following treatment with nanoceria in different gravity regimes.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 134 Downloadable Samples
Illumina HiSeq 2500, Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
Transcriptional regulatory networks (TRNs) provide insight into cellular behavior by describing interactions between transcription factors (TFs) and their gene targets. The Assay for Transposase Accessible Chromatin (ATAC)-seq, coupled with transcription-factor motif analysis, provides indirect evidence of chromatin binding for hundreds of TFs genome-wide. Here, we propose methods for TRN inference in a mammalian setting, using ATAC-seq data to influence gene expression modeling. We rigorously test our methods in the context of T Helper Cell Type 17 (Th17) differentiation, generating new ATAC-seq data to complement existing Th17 genomic resources (plentiful gene expression data, TF knock-outs and ChIP-seq experiments). In this resource-rich mammalian setting our extensive benchmarking provides quantitative, genome-scale evaluation of TRN inference combining ATAC-seq and RNA-seq data. We refine and extend our previous Th17 TRN, using our new TRN inference methods to integrate all Th17 data (gene expression, ATAC-seq, TF KO, ChIP-seq). We highlight new roles for individual TFs and groups of TFs (“TF-TF modules”) in Th17 gene regulation. Given the popularity of ATAC-seq (a widely adapted protocol with high resolution and low sample input requirements), we anticipate that application of our methods will improve TRN inference in new mammalian systems and be of particular use for rare, uncharacterized cell types. Overall design: Gene expression (RNA-seq) of naive and Th17- and Th0-polarized CD4 T Cells
Publication Title
Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina Genome Analyzer II
Description
Here we describe microRNA profiling of a single differentiation pathway from the stem cell through to terminally differentated mature cells. Overall design: Populations corresponding to distinct stages in T lymphocyte development, from the hematopoietic stem cell-enriched Lin-Sca+Kit+ population through to mature CD4+ and CD8+ T cells were FACS-sorted to purity from the bone marrow and thymus of C57BL/6 mice. Total RNA was extract from each population from which microRNA sequencing libraries were constructed.
Publication Title
Dynamic microRNA gene transcription and processing during T cell development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer II
Description
Here we show the microRNA genes can been very large and displaying many summarizing structural characteristics Overall design: MicroRNA biogenesis was ablated in CD4+ and CD8+ by deleted Rnasen gene (encoding Drosha). Poly A RNAs were extracted and analyzed by ultra high throughput sequencing
Publication Title
Dynamic microRNA gene transcription and processing during T cell development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD4+ T helper lymphocytes that express interleukin-17 (Th17 cells) have critical roles in mouse models of autoimmunity, and there is mounting evidence that they also influence inflammatory processes in humans. Genome-wide association studies in humans have linked genes involved in Th17 cell differentiation and function with susceptibility to Crohns disease, rheumatoid arthritis, and psoriasis1-3. Thus, the pathway towards differentiation of Th17 cells and, perhaps, of related innate lymphoid cells with similar effector functions4, 5, is an attractive target for therapeutic applications. Mouse and human Th17 cells are distinguished by expression of the retinoic acid receptor-related orphan nuclear receptor RORt, which is required for induction of IL-17 transcription and for the manifestation of Th17-dependent autoimmune disease in mice6. By performing a chemical screen with an insect cell-based reporter system, we identified the cardiac glycoside digoxin as a specific inhibitor of RORt transcriptional activity. Digoxin inhibited murine Th17 cell differentiation without affecting differentiation of other T cell lineages and was effective in delaying the onset and reducing the severity of autoimmune disease in mice. At high concentrations, digoxin is toxic for human cells, but non-toxic synthetic derivatives, 20,22-dihydrodigoxin-21,23-diol (Dig(dhd)) and digoxin-21-salicylidene (Dig(sal)), specifically inhibited induction of IL-17 in human CD4+ T cells. Using these small molecule compounds, we demonstrated that RORt is imporant for the maintenance of IL-17 expression in mouse and human effector T cells. These data suggest that derivatives of digoxin can be used as chemical probes for development of RORt-targeted therapeutic agents that attenuate inflammatory lymphocyte function and autoimmune disease.
Publication Title
Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors (GSI), which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Analysis of gene expression in GSI-responsive and GSI-resistant cell lines treated with Compound E identifies differential resopnses to GSI.
Publication Title
Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors, which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Here we show that NOTCH1 regulates PTEN expression and the activity of the PI3K-AKT signaling pathway in normal and leukemic T cells. Notch signaling and the PI3K-AKT pathway synergize in vivo in a Drosophila model of Notch-induced tumorigenesis, and mutational loss of PTEN is associated with increased glycolysis and resistance to NOTCH1 inhibition in human T-ALL. These findings identify the transcriptional regulation of PTEN and the control of cellular metabolism as key elements of the oncogenic program activated by NOTCH1 and provide the basis for the design of new therapeutic strategies for T-ALL.
Publication Title
Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 50 Downloadable Samples
- Illumina HiSeq 2000
Description
We perform RNA sequencing and ribosome profiling time course experiments to examine the effect of fully dysregulating all let-7 targets (in let-7(n2853) animals), partially dysregulating only LIN41 (in lin-41(xe11) animals) or fully dysregulating all let-7 targets while partially dysregulating LIN41 in lin-41(xe11); let-7(n2853) double mutant animals. We conclude that effects on gene expression in let-7 mutant animals are largely and quantitatively explained by dysregulation of LIN41 as its primary target. Furthermore, we identify direct LIN41 target genes regulated on the level of translation or mRNA abundance. Overall design: Total RNA-sequencing time course experiments sampling synchronized worm populations of different genetic backgrounds every two hours over the course of development from late L2/early L3 stage to late L4/Young adult stage.
Publication Title
LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 45 Downloadable Samples
- Illumina HiSeq 2000
Description
We perform RNA sequencing and ribosome profiling time course experiments to examine the effect of fully dysregulating all let-7 targets (in let-7(n2853) animals), partially dysregulating only LIN41 (in lin-41(xe11) animals) or fully dysregulating all let-7 targets while partially dysregulating LIN41 in lin-41(xe11); let-7(n2853) double mutant animals. We conclude that effects on gene expression in let-7 mutant animals are largely and quantitatively explained by dysregulation of LIN41 as its primary target. Furthermore, we identify direct LIN41 target genes regulated on the level of translation or mRNA abundance. Overall design: Ribosome profiling time course experiments sampling synchronized worm populations of different genetic backgrounds every two hours over the course of development from late L2/early L3 stage to late L4/Young adult stage.
Publication Title
LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 15 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
RNA-binding proteins (RBPs) are critical regulators of gene expression and elucidating the interactions of RBPs with their RNA targets is necessary to understand how combinations of RBPs control transcriptome expression. The Quaking-related (QR) sub-family of STAR domain RBPs includes developmental regulators and tumor suppressors such as C. elegans GLD-1, which functions as a master regulator of germ line development. To understand how GLD-1 interacts with the transcriptome, we identified GLD-1 associated mRNAs by a ribonomic approach. The scale of GLD-1 mRNA interactions allowed us to determine rules governing GLD-1 target selection and to derive a predictive model where GLD-1 association with mRNA is based on the number and strength of 7-mer GLD-1 binding elements (GBEs) within UTRs. GLD-1/mRNA interactions were quantified, and predictions were verified both in vitro and in live animals, including by transplantation experiments where weak and strong GBEs imposed translational repression of increasing strength on a non-target mRNA.Importantly, this study provides a unique quantitative picture of how an RBP interacts with its mRNA targets. As combinatorial regulation by multiple RBPs is thought to regulate gene expression, quantification of RBP/mRNA interactions should be a way to predict and potentially modify biological outcomes of complex posttranscriptional regulatory networks, and our analysis suggests that such an approach is possible.
Publication Title
A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1.
Sample Metadata Fields
Specimen part
View Samples