We used zebrafish embryos as an in vivo system to investigate the role of the microRNA-146 family (consisting of 2 members miR-146a and miR-146b) in the innate immune response to S. typhimurium infection. To determine the role of miR-146 microRNAs in the response to S. typhimurium infection we used Illumina RNA sequencing to compare the mRNA expression profiles of control embryos versus embryos with knockdown of miR-146a and miR-146b. RNA sequencing analysis of miR-146 knockdown embryos showed no major effects on pro-inflammatory gene expression or on the expression of transcriptional regulators and signal transduction components of the immune response. In contrast, apoliprotein-mediated lipid transport emerged as an infection-inducible pathway under miR-146 knockdown conditions, suggesting a function of miR-146 in regulating lipid metabolism during inflammation. Overall design: Embryos were injected at the one cell stage with a combination of two morpholinos targeting miR-146a and miR-146b, or with the standard control morpholino from GeneTools. Subsequently, at 28 hours post fertilzation (hpf) they were infected by injecting 200-250 colony forming units of S. typhimurium strain SL1027 into the caudal vein, or mock-injected with PBS. RNA was isolated at 8 hours post injection (hpi) for Illumina RNAseq analysis. Two independent experiments were performed for RNAseq analysis of biological duplicates.
MicroRNA-146 function in the innate immune transcriptome response of zebrafish embryos to Salmonella typhimurium infection.
No sample metadata fields
View SamplesWe used different zebrafish transgenic lines to sort macrophages, neutrophils and immature lymphoid cells from 5-6 day old zebrafish larvae and analyzed their transcriptomes. Comparison between the different transcriptomes and gene ontology analysis revealed specificities for each cell population. Comparison with previously published data showed that zebrafish larval macrophages expressed several known human M1 and M2 macrophages. Transcriptome analysis of uninfected and infected macrophages from embryos infected by of Mycobacterium marinum revealed infection induced transcriptional changes and a shift towards M1 transcriptomic signature. Overall design: Embryos were grown into egg water refresh every day and incubated for 5 or 6 days at 28°C. 0.003% 1-phenyl-2-thiourea (Sigma-Aldrich) was added after 1 day to prevent melanisation. After the incubation period, embryos were dissociated into single cell suspension by Trypsin treatment and fluorescent cells were sorted by FACS. RNA extraction and library preparation were performed as previously described. (Rougeot et al., 2014, Methods Mol Biol 1197:41-66). For infection experiments, zebrafish embryos were manually dechorionated at 24 hours post fertilization (hpf) and were infected by injection in the caudal vein of 125 colony forming unit of Mycobacterium marinum M strain expressing GFP. Infected larvae were collected for FACS sorting 5 day post infection.
Corrigendum: RNAseq Profiling of Leukocyte Populations in Zebrafish Larvae Reveals a <i>cxcl11</i> Chemokine Gene as a Marker of Macrophage Polarization During Mycobacterial Infection.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Specimen part, Cell line
View SamplesA genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Cell line
View SamplesA genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Cell line
View SamplesA genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Specimen part
View SamplesPotassium is one of the essential macronutrients required for plant growth and development. It plays a major role in different physiological processes like cell elongation, stomatal movement, turgor regulation, osmotic adjustment, and signal transduction by acting as a major osmolyte and component of the ionic environment in the cytosol and subcellular organelles.
Gene expression analysis of rice seedling under potassium deprivation reveals major changes in metabolism and signaling components.
Specimen part, Treatment, Time
View SamplesInvestigation of mRNA changes in podocytes transfected with a miR-93 mimic or a nontargeting mimic. Overall design: The design was meant to identify biologically significant, novel targets of the miR-93 microRNA in podocytes
miR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy.
No sample metadata fields
View SamplesImmunosuppression is needed in HLA identical sibling renal transplantation. We conducted a tolerance trial in this patient cohort using Alemtuzumab induction, donor hematopoietic stem cells, tacrolimus/mycophenolate immunosuppression converted to sirolimus, planning complete drug withdrawal by 24 months post-transplantation. After an additional 12 months with no immunosuppression, normal biopsies and renal function, recipients were considered tolerant. Twenty recipients were enrolled. Of the first 10 (>36 months post-transplantation), 5 had immunosuppression successfully withdrawn for 16-36 months (tolerant), 2 had disease recurrence and 3 had subclinical rejection in protocol biopsies (non-tolerant). Microchimerism disappeared after 1 year, and CD4+CD25highCD127-FOXP3+ T cells and CD19+IgD/M+CD27- B cells increased to 5 years post-transplantation in both groups, whereas immune/inflammatory gene expression pathways in the peripheral blood and urine were differentially downregulated in tolerant compared to non-tolerant recipients. Therefore, in this HLA identical renal transplant tolerance trial, absent chimerism, Treg and Breg immunophenotypes were indistinguishable between tolerant and non-tolerant recipients, but global genomic changes indicating immunomodulation were observed only in tolerant recipients.
Genomic biomarkers correlate with HLA-identical renal transplant tolerance.
Specimen part, Time
View SamplesPhosphatidylcholine transfer protein (PC-TP, a.k.a StarD2) is abundantly expressed in liver and is regulated by PPAR. When fed the synthetic PPAR ligand fenofibrate, Pctp-/- mice exhibited altered lipid and glucose homeostasis. Microarray profiling of liver from fenofibrate fed wild type and Pctp-/- mice revealed differential expression of a broad array of metabolic genes, as well as their regulatory transcription factors. Because its expression controlled the transcriptional activities of both PPAR and HNF4 in cell culture, the broader impact of PC-TP on nutrient metabolism is most likely secondary to its role in fatty acid metabolism.
Regulatory role for phosphatidylcholine transfer protein/StarD2 in the metabolic response to peroxisome proliferator activated receptor alpha (PPARalpha).
Sex, Age, Specimen part
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