Transfer RNA (tRNA) modifications enhance the efficiency, specificity and fidelity of translation in all organisms. The anticodon modification mcm5s2U34 is required for normal growth and stress resistance in yeast; mutants lacking this modification have numerous phenotypes. Mutations in the homologous human genes are linked to neurological disease. The yeast phenotypes can be ameliorated by overexpression of specific tRNAs, suggesting that the modifications are necessary for efficient translation of specific codons. We determined the in vivo ribosome distributions at single codon resolution in yeast strains lacking mcm5s2U. We found accumulations at AAA, CAA, and GAA codons, suggesting that translation is slow when these codons are in the ribosomal A site, but these changes appeared too small to affect protein output. Instead, we observed activation of the GCN4-mediated stress response by a non- canonical pathway. Thus, loss of mcm5s2U causes global effects on gene expression due to perturbation of cellular signaling. Overall design: WT yeast and mutants lacking anticodon tRNA modifications were grown in YPD, and subjected to ribosome footprint profiling (ribo-seq) and RNA-seq of poly-A selected RNA. Dataset contains biological replicates for WT, ?ncs6 and ?uba4. Technical replicates were also performed for all RNA-seq datasets (using a different poly-A selection method).
Loss of a conserved tRNA anticodon modification perturbs cellular signaling.
Cell line, Subject
View SamplesRON WT and RON KO at 5, 6, 7 week virgin mammary glands
The Ron receptor tyrosine kinase negatively regulates mammary gland branching morphogenesis.
Age
View SamplesTo understand the molecular control of development and regeneration in the mammalian cochlear sensory epithelia, we performed a comparative study of gene expression patterns between postnatal day-3 (P3) and adult stages using a microarrays approach.
Transcriptomic analysis of the developing and adult mouse cochlear sensory epithelia.
Specimen part
View SamplesWe examined the role of TREM2 on microglia responses to amyloid-beta deposition in a mouse model of Alzheimer's disease
TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model.
Age, Specimen part
View SamplesBackground: MYC is a transcription factor encoded by the c-MYC gene (thereafter termed MYC). MYC is key transcription factor involved in many central cellular processes including ribosomal biogenesis. MYC is overexpressed in the majority of human tumours including aggressive B-cell lymphoma especially Burkitt's lymphoma. Although Burkitt's lymphoma is a highlight example for MYC overexpression due to a chromosomal translocation, no global analysis of MYC binding sites by chromatin immunoprecipitation (ChIP) followed by global next generation sequencing (ChIP-Seq) has been conducted so far in Burkitt's lymphoma.
Deep sequencing of MYC DNA-binding sites in Burkitt lymphoma.
Specimen part, Cell line
View Samples10 adult participants of dose group 3x10^6 pfu, and 10 participants of dose group 20x10^6 pfu. Reads were aligned to the human reference assembly (GRCh38.p7) using STAR software (v2.4.2a; option ''--quantMode GeneCounts''). Gene annotation was obtained from Ensembl (release 79, ensemble.org). VOOM+Limma analysis (R software, version 3.2.2) was used to assess differential gene expression at each post-vaccination day (d1, d3 and d7) against baseline (d0). Next, we intergreted gene expression data and antibody response using an sPLS algorithm, in order to down-select genes correlating with multivariate antibody responses at days 28, 54, 84,180. Overall design: 56 samples from D0, D1, D3 and D7 were analysed. Data from samples with low RIN (RIN <8, 17 samples), low RNA or library concentration (2 samples), missing samples (5 samples) were set to missing.
Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV.
Specimen part, Subject
View SamplesClassical dendritic cells (DCs) are key players at the interface between innate and adaptive immunity. In the kidney exist 2 major subsets of cDCs: CD11b+ cDCs and CD103+ cDCs. We investigated their function in the most widely used model of experimental glomerulonephritis (GN) in mice: nephrotoxic nephritis (NTN). Consistent with a role for cDCs in nephrotoxic nephritis, depletion of ZBTB46+ cells (all cDCs) attenuated kidney injury, while deficiency of the CD103+ subset of cDCs accelerated injury via a mechanism that involved increased neutrophils. This RNAseq was performed to analyze transcriptional changes in FACS-sorted renal CD11b+ and CD103+ cDCs under healthy conditions and at day 7 of NTN to reveal why both subsets have different functions in GN. Overall design: The study was performed with total of 6 mice (wildtype, male, age 8-12 weeks). 3 mice were sacrificed in the healthy situation, 3 mice were sacrificed 7 days after injection of the nephrotoxic nephritis antiserum (NTN). From each mouse CD11b+ and CD103+ DCs were sorted, resulting in 4 experimental conditions with 3 biological replicates each: CD103_healthy, CD11b_healthy, CD103_NTN, CD11b_NTN.
Opposing Roles of Dendritic Cell Subsets in Experimental GN.
Sex, Specimen part, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans.
Sex, Age, Specimen part, Disease, Race, Subject
View SamplesTranslational Relevance
Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans.
Sex, Age, Race, Subject
View SamplesThe morphogen and mitogen, Sonic Hedgehog, activates a Gli1-dependent transcription program that drives proliferation of granule neuron progenitors (GNPs) within the external germinal layer of the postnatally developing cerebellum. Medulloblastomas with mutations activating the Sonic Hedgehog signaling pathway preferentially arise within the external germinal layer, and the tumor cells closely resemble GNPs. Atoh1/Math1, a basic helix-loop-helix transcription factor essential for GNP histogenesis, does not induce medulloblastomas when expressed in primary mouse GNPs that are explanted from the early postnatal cerebellum and transplanted back into the brains of nave mice. However, enforced expression of Atoh1 in primary GNPs enhances the oncogenicity of cells overexpressing Gli1 by almost three orders of magnitude. Unlike Gli1, Atoh1 cannot support GNP proliferation in the absence of Sonic Hedgehog signaling and does not govern expression of canonical cell cycle genes. Instead, Atoh1 maintains GNPs in a Sonic Hedgehog-responsive state by regulating genes that trigger neuronal differentiation, including many expressed in response to bone morphogenic protein-4. Therefore, by targeting multiple genes regulating the differentiation state of GNPs, Atoh1 collaborates with the pro-proliferative Gli1-dependent transcriptional program to influence medulloblastoma development.
Atoh1 inhibits neuronal differentiation and collaborates with Gli1 to generate medulloblastoma-initiating cells.
Age, Specimen part, Treatment
View Samples