The type I JAK inhibitor ruxolitinib is approved for therapy of MPN patients but evokes resistance with longer exposure. Several novel type I JAK inhibitors were studied and we show that they uniformly induce resistance via a shared mechanism of JAK family heterodimer formation.Here we studied the expression profiles of SET2 cell lines persistent to several different type I JAK inhibitors in comparison to naive SET2 cells or in comparison to SET2 cells with acute exposure to ruxolitinib. Overall design: Analysis of RNA isolated from several type I JAK inhibitor SET2 cell lines in comparison to naïve SET2 cells
CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms.
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View SamplesStressors may have negative or positive effects in dependence of the dose (hormesis). We studied this phenomenon in Caenorhabditis elegans by applying weak or severe abiotic (cadmium, CdCl2) and/or biotic stress (different bacterial diets) during cultivation/breeding of the worms, and determining developmental speed or survival rates and performing transcriptome profiling and RT-qPCR analyses to explore the genetic basis of the detected phenotypic differences. This study showed that a bacterial diet resulting in higher levels of energy resources in the worms (E. coli OP50 feeding) or weak abiotic and biotic stress especially promote the resistance against severe abiotic or biotic stress and the age-specific survival rate of WT. Overall design: Five experimental conditions; mostly three replicates per experimental condition; four contrasts between test and control conditions functionally analyzed.
Bacterial diet and weak cadmium stress affect the survivability of <i>Caenorhabditis elegans</i> and its resistance to severe stress.
Cell line, Treatment, Subject
View SamplesAGO-PAR-CLIP was employed to identify microRNA binding sites in BCBL-1, a Kaposi's sarcoma-associated herpesvirus (KSHV) infected B-cell line and DG75, a KSHV negative B-cell line as a control. By using our novel computational method (PARma) and differential analysis of PAR-CLIP data, highly accurate target sites of KSHV microRNAs can be defined. Overall design: Examination of microRNA target sites in two different cell lines using replicate PAR-CLIP experiments
PARma: identification of microRNA target sites in AGO-PAR-CLIP data.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Conserved principles of mammalian transcriptional regulation revealed by RNA half-life.
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View SamplesData from tc-, nt- and p-RNA as well as 1 and 2h of actinomycin-D treatment (5g/ml) of NIH-3T3 cells used to determine half-lives. RNA was labeled for 15, 30 or 60 minutes with 4-thiouridine. After preparation of tc-RNA, thiol-labeled RNA was biotinylated using biot-HPDP and subsequently tc-RNA was separated into nt- and p-RNA using streptavidin coated magnetic beads. All three fractions were used for microarray analysis. For actinomycin-D experiments only tc-RNA was used prepared from cell before and 1 an 2h after addition of act-D.
Conserved principles of mammalian transcriptional regulation revealed by RNA half-life.
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View SamplesRNA was labeled in BL41 cells by culturing cells for 60 min in media containing 100M 4sU. Tc-RNA was separated into nt- and p-RNA. All three RNA subsets were subjected to microarray analysis. Only probe sets providing present calls in all RNA samples/subsets were included into the analysis
Conserved principles of mammalian transcriptional regulation revealed by RNA half-life.
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View SamplesTranscript abundance results from the balance between transcription and mRNA decay, and varies pervasively in humans. We have examined the effect of DNA variation on mRNA half-life differences by conducting a genome-wide survey of mRNA stability in seven human HapMap lymphoblastoid cell lines (LCLs). We determined the mRNA half-life for each gene from the ratio of 4-thio-uridine (4sU)-labeled nascent RNAs to total RNAs. 5,145 (46%) of 11,132 analyzed genes showed inter-individual mRNA half-life differences at a false discovery rate, FDR<0.05. As previously reported, we found transcription to be the main factor influencing transcript abundance. Although mRNA half-life explained only ~6% of transcript abundance on average, it explained ~16% for the subset of genes (~10%) showing inter-individual mRNA half-life differences (P<0.001). We confirmed previously reported correlations of mRNA half-life with transcript length, 3-UTR length, and number of exon-junctions per kb of transcript. The number of miRNA targets in 3-UTRs was negatively correlated with half-life (P=2.210-16), a new observation that is consistent with the role of miRNA in inducing mRNA degradation. Notably, coding GC and GC3 content showed positive correlations with mRNA half-life in genes with inter-individual mRNA half-life differences, implying a role of mRNA stability in shaping synonymous codon usage bias. Consistently, G or C alleles of coding SNPs were found associated with longer mRNA half-life (P=0.021). As expected, we also found that nonsense SNPs were associated with shorter mRNA half-life (P=0.009). Our results strongly suggest that inter-individual mRNA stability differences are widespread and affected by DNA sequence and composition variation.
Genome-wide survey of interindividual differences of RNA stability in human lymphoblastoid cell lines.
Disease, Cell line
View SamplesExpression data from NIH-3T3 cells treated with mock, 100 U/ml IFN alpha or 100 U/ml gamma for 1 or 3h on nt-RNA labeled for 30-60 min at different times of interferon treatment
High-resolution gene expression profiling for simultaneous kinetic parameter analysis of RNA synthesis and decay.
No sample metadata fields
View SamplesPrimary human foreskin fibroblasts (HFF) were infected with wild-type simplex virus 1 (HSV-1) strain 17 at a multiplicity of infection (MOI) of 10. Ribosome profiling was performed at various times during infection with minor modification to the protocol described in Stern-Ginossar N et al., Science 2012 Overall design: Ribosome profiling was performed a 0, 1, 2, 4, 6 and 8 h post infection. Two biological replicates were analysed.
Widespread disruption of host transcription termination in HSV-1 infection.
No sample metadata fields
View SamplesDifferential gene expression caused by 1h and 3h of IFN alpha or gamma treatment was analyzed in total cellular RNA of NIH-3T3 cells compared to mock
High-resolution gene expression profiling for simultaneous kinetic parameter analysis of RNA synthesis and decay.
No sample metadata fields
View Samples