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GSE68091
Homo sapiens
28 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The small molecule ONC201 is toxic in vitro to multiple cell lines and primary tumor samples of mantle cell lymphoma (MCL) and acute myeloid leukemia, even ones with unfavorable genetic features (notably including TP53 inactivation) or acquired resistance to other agents. Because the mechanism of action in these malignant hematologic cells appeared to differ from that in solid tumors, we performed gene expression profiling (GEP) studies on MCL lines treated with ONC201 and other agents with known mechanisms of action. Treatment of JeKo-1 cells with 5 uM ONC201 showed consistent and progressive increases or decreases over time in two sets of genes: upregulated genes, which implicated an ER stress response and mTOR pathway inhibition, and downregulated genes, which implicated reduced proliferation. These implicated effects of ONC201 were validated by confirmatory experiments. Similar GEP changes were observed in ONC201-naive Z138 cells after 24 hr of ONC201 treatment, but were not seen in Z138 cells made ONC201-resistant by chronic exposure. Finally, the GEP effects of ONC201 in JeKo-1 cells were mimicked by the ER stress inducer tunicamycin, but not by the direct MTOR inhibition rapamycin, further confirming an ER stress response and suggesting that inhibition of the mTOR pathway was by an indirect mechanism.
Publication Title
ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
mRNA from bone marrow-derived MSCs stably expressing CTGF-specific shRNA (or empty vector control) was analyzed for differential gene expression. Significant differences were found in cell proliferation-related genes, especially genes related to the M phase of the cell cycle, which were down-regulated in CTGF-knockdown-MSCs compared to control MSCs.
Publication Title
Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
We analyzed the C. elegans small RNA response to high copy transgene sequences expressed in the soma in a wild type and an eri-6/7 mutant background. We also analyzed small RNA defects in the arl-8(tm2472) mutant. Transgene siRNAs are 22 nt long, mostly antisense, and correspond to the promoter, coding regions, the 3''UTR and plamsid sequences present on the transgene. Transgene siRNAs are decreased in the eri-6/7 mutant. In the arl-8 mutant, 26G siRNAs in the ALG-3/4 dependent endogenous RNAi pathway are decreased. Overall design: Sequencing small RNAs from C. elegans transgenic strains and mutants.
Publication Title
Multiple small RNA pathways regulate the silencing of repeated and foreign genes in C. elegans.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Caenorhabditis elegans
- 7 Downloadable Samples
- Illumina Genome Analyzer II
Description
To characterize the role of the ERI-6/7 helicase in endogenous small RNA pathways in C. elegans, small RNA populations from null alleles of eri-6 and eri-7, and from mutants of known endogenous RNAi pathway factors, eri-1 and ergo-1, were determined by deep sequencing, and compared to wild type. Overall design: Small RNA analysis in wild type and eri-1, ergo-1, eri-6 and eri-7 mutant C. elegans strains.
Publication Title
The ERI-6/7 helicase acts at the first stage of an siRNA amplification pathway that targets recent gene duplications.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 5 Downloadable Samples
- Illumina Genome Analyzer II
Description
Argonaute-associated siRNAs and Piwi-associated piRNAs have overlapping roles in silencing mobile genetic elements in animals. In C. elegans, mutator-class (mut) genes mediate siRNA-guided repression of transposons as well as exogenous RNA-directed gene silencing (RNAi), but their roles in endogenous RNA silencing pathways are not well understood. To characterize the endogenous small RNAs dependent on mutator-class genes, small RNA populations from a null allele of mut-16, as well as a regulatory mut-16(mg461) allele that disables only somatic RNAi, were subjected to deep sequencing. Overall design: Small RNA analysis in wild type and mut-16 mutant C. elegans strains
Publication Title
mut-16 and other mutator class genes modulate 22G and 26G siRNA pathways in Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 19 Downloadable Samples
- Illumina HiSeq 2000
Description
This data series contains small RNA high-throughput sequencing data for each of the mutator class genes. Samples are from stage-matched adult C. elegans grown at 20°C. Overall design: Small RNAs were isolated from synchronized wild type and mutant C. elegans and subjected to Illumina HiSeq sequencing. The series contains fastq and tab-separated files for 19 libraries.
Publication Title
MUT-14 and SMUT-1 DEAD box RNA helicases have overlapping roles in germline RNAi and endogenous siRNA formation.
Sample Metadata Fields
Cell line, Subject
View Samples- Saccharomyces cerevisiae
- 56 Downloadable Samples
- Illumina HiSeq 2500, Illumina MiSeq, Illumina HiSeq 2000
Description
N6-methyladenosine (m6A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m6A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 putatively methylated sites within 1,183 transcripts. We validated 8/8 methylation sites in different genes with direct genetic analysis, demonstrated that methylated sites are significantly conserved in a related species, and built a model that predicts methylated sites directly from sequence. Sites vary in their methylation profiles along a dense meiotic time-course, and are regulated both locally, via predictable methylatability of each site, and globally, through the core meiotic circuitry. The methyltransferase complex components localize to the yeast nucleolus, and this localization is essential for mRNA methylation. Our data illuminates a conserved, dynamically regulated methylation program in yeast meiosis, and provides an important resource for studying the function of this epitranscriptomic modification. Overall design: Examination of m6A methylation under various conditions
Publication Title
High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis.
Sample Metadata Fields
Cell line, Subject
View Samples