To investigate whether C. parvum treatment of DCs regulates other inflammatory genes, mouse BMDCs (CD11c and CD11b positive) were treated with C. parvum for 24 hr. Control groups included untreated BMDCs and DCs treated with E. cuniculi. We noticed that a significant upregulation of the expression of interferon-related genes, which may correlation the critical role of interferon in host defense against C. parvum infection.
No associated publication
Sex, Specimen part
View SamplesIKK kinase is essential for the B cell maturation and secondary lymphoid organ development. In the current study, we evaluated the role of IKK in the marginal zone and follicular B lymphocyte development by genetically deleting IKK from the B cell lineage using CD19-Cre mice. The loss of IKK did not affect the normal development of early B cell progenitors. However, a significant decline was observed in the percentage of immature B lymphocytes, mature marginal zone and follicular B cells along with a severe disruption of splenic marginal and follicular B cell zones. A gene expression analysis performed on the RNA extracted from the newly formed B cells (B220+IgMhi) revealed that IKK deficiency produces significant changes in the expression of genes involved in MZ and FO B lymphocyte survival, homing and migration. And several among those genes identified belong to G protein family. Specifically, we validated the upregulated expression of regulator of G protein signaling 13 (RGS13), which is a GTPase activating protein (GAP) that negatively regulates G protein signaling and impede B cell migration. Likewise, promigratory B lymphocyte receptor, the sphingosine-1-phosphate receptor 3 (SIPR3) that couple to Gi showed significantly reduced expression. In addition, an in silico analysis of gene product interactions revealed NF-B signaling pathways to be a major gene regulating networks perturbed with IKK deletion. Taken together, this study reveals IKKNF-B and G protein signaling axis to be central for the MZ and FO B cells survival, maintenance, homing and migration.
IKKα deficiency disrupts the development of marginal zone and follicular B cells.
Specimen part
View SamplesEfferent inhibition of cochlear outer hair cells is mediated by nicotinic cholinergic receptors containing alpha9 (a9) and alpha10 subunits. Mice lacking a9 nicotinic subunits fail to exhibit classic olivocochlear responses and are characterized by abnormal synaptic morphology at the base of outer hair cells. To detail molecular changes induced upon the loss of a9 subunit, we sampled cochlear RNA from wild type and a9 null mice at postnatal (P) days spanning periods of synapse formation and maturation (P3, P7, P13 and P60). Our findings point to a delay in cochlear maturation starting at the onset of hearing (P13), as well as an up-regulation of various GABA receptor subunits in adult mice lacking the a9 nicotinic subunit.
Lack of nAChR activity depresses cochlear maturation and up-regulates GABA system components: temporal profiling of gene expression in alpha9 null mice.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Specimen part, Compound
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrating factor analysis and a transgenic mouse model to reveal a peripheral blood predictor of breast tumors.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.
Sex, Age, Disease stage, Race
View SamplesThe well-defined battery of in vitro systems applied within chemical cancer risk assessment is often characterised by a high false-positive rate, thus repeatedly failing to correctly predict the in vivo genotoxic and carcinogenic properties of test compounds. Toxicogenomics, i.e. mRNA-profiling, has been proven successful in improving the prediction of genotoxicity in vivo and the understanding of underlying mechanisms. Recently, microRNAs have been discovered as post-transcriptional regulators of mRNAs. It is thus hypothesised that using microRNA response-patterns may further improve current prediction methods. This study aimed at predicting genotoxicity and non-genotoxic carcinogenicity in vivo, by comparing microRNA- and mRNA-based profiles, using a frequently applied in vitro liver model and exposing this to a range of well-chosen prototypical carcinogens. Primary mouse hepatocytes (PMH) were treated for 24 and 48h with 21 chemical compounds [genotoxins (GTX) vs. non-genotoxins (NGTX) and non-genotoxic carcinogens (NGTX-C) versus non-carcinogens (NC)]. MicroRNA and mRNA expression changes were analysed by means of Exiqon and Affymetrix microarray-platforms, respectively. Classification was performed by using Prediction Analysis for Microarrays (PAM). Compounds were randomly assigned to training and validation sets (repeated 10 times). Before prediction analysis, pre-selection of microRNAs and mRNAs was performed by using a leave-one-out t-test. No microRNAs could be identified that accurately predicted genotoxicity or non-genotoxic carcinogenicity in vivo. However, mRNAs could be detected which appeared reliable in predicting genotoxicity in vivo after 24h (7 genes) and 48h (2 genes) of exposure (accuracy: 90% and 93%, sensitivity: 65% and 75%, specificity: 100% and 100%). Tributylinoxide and para-Cresidine were misclassified. Also, mRNAs were identified capable of classifying NGTX-C after 24h (5 genes) as well as after 48h (3 genes) of treatment (accuracy: 78% and 88%, sensitivity: 83% and 83%, specificity: 75% and 93%). Wy-14,643, phenobarbital and ampicillin trihydrate were misclassified. We conclude that genotoxicity and non-genotoxic carcinogenicity probably cannot be accurately predicted based on microRNA profiles. Overall, transcript-based prediction analyses appeared to clearly outperform microRNA-based analyses.
Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Specimen part, Compound
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Evaluating microRNA profiles reveals discriminative responses following genotoxic or non-genotoxic carcinogen exposure in primary mouse hepatocytes.
Specimen part, Compound
View SamplesSpecification of germ cell fate is fundamental in development. With a highly representative single-cell microarray and rigorous quantitative-PCR analysis, we defined the genome-wide transcription dynamics that create primordial germ cells (PGCs) from the epiblast, a process that exclusively segregates them from their somatic neighbors. We also analyzed the effect of the loss of Blimp1, a key transcriptional regulator, on these dynamics. Our analysis revealed that PGC specification involves complex, yet highly ordered regulation of a large number of genes, proceeding under the strong influence of mesoderm induction with active repression of specific programs such as epithelial-mesenchymal transition, Hox gene activation, cell-cycle progression and DNA methyltransferase machinery. Remarkably, Blimp1 is essential for repressing nearly all the genes normally down-regulated in PGCs relative to their somatic neighbors, whereas it is dispensable for the activation of approximately half of the genes up-regulated in PGCs.
No associated publication
No sample metadata fields
View SamplesGene expression profiling using microarray has been limited to profiling of differentially expressed genes at comparison setting since probesets for different genes have different sensitivities. We overcome this limitation by using a very large number of varied microarray datasets as a common reference, so that statistical attributes of each probeset, such as dynamic range or a threshold between low and high expression can be reliably discovered through meta-analysis. This strategy is implemented in web-based platform named Gene Expression Commons (http://gexc.stanford.edu/ ) with datasets of 39 distinct highly purified mouse hematopoietic stem/progenitor/functional cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, any scientist can explore gene expression of any gene, search by expression pattern of interest, submit their own microarray datasets, and design their own working models.
Gene Expression Commons: an open platform for absolute gene expression profiling.
Sex, Age
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