There is high need of novel diagnostic and prognostic tools for tumors of the digestive system, such as gastric cancer and cholangiocarcinoma.
MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer.
Specimen part
View SamplesPompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study, we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease.
Transcriptional response to GAA deficiency (Pompe disease) in infantile-onset patients.
Sex, Specimen part, Disease, Treatment, Subject
View SamplesWe 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.
LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms.
Cell line, Subject
View SamplesWe 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.
LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms.
Cell line, Subject
View SamplesRNA-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.
A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1.
Specimen part
View SamplesThe goal was to identify targets of the RNase REGE-1 by whole RNA sequencing. Overall design: mRNA profiling of C.elegans young adults of rege-1 knockdown or mock RNAi control performed in N2 as well as glp-1 background
Ribonuclease-Mediated Control of Body Fat.
Cell line, Subject
View SamplesEts-4 was previously identified as a suppressor of rege-1(rrr13) phenotype. The goal of this experiment was to identify down-stream regulators of ETS-4, which facilitate this suppression. Overall design: mRNA profiling of C.elegans young adults of ets-4 knockdown or mock RNAi control in the background of rege-1(rrr13)
Ribonuclease-Mediated Control of Body Fat.
Cell line, Subject
View SamplesWe present a basic characterization of the function of Y-box binding proteins in C. elegans. Besides playing an important role for fertility in the germline (all four CEY proteins), we found that the presence of CEY-1 and CEY-4 is essential for the assembly of larger polysomes in the soma. We therefore performed ribosome-profiling in combination with total RNA sequencing in wild type and cey-1,-4 double mutant animals to globally compare mRNA levels and their translation status. Overall design: Total RNA sequencing was peformed on RNA extacted from wild type and cey-1,-4 mutant animals in duplicates. Four samples in total.
Functional characterization of C. elegans Y-box-binding proteins reveals tissue-specific functions and a critical role in the formation of polysomes.
Cell line, Subject
View SamplesTo identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone (Crh), the GABA transporter (Slc6a1), and prodynorphin (Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G15 coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr, and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Further, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.
Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum.
No sample metadata fields
View SamplesGene expression of P. aerruginosa changes after short-term exposure to ciprofloxacin at sub-inhibitory concentrations but the effect of long-term exposure which select for the most fitted subpopulations is not known.
The phenotypic evolution of Pseudomonas aeruginosa populations changes in the presence of subinhibitory concentrations of ciprofloxacin.
No sample metadata fields
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