Background: MicroRNAs (miRNAs) are a family of small, non-coding single-stranded RNA molecules involved in post-transcriptional regulation of gene expression. As such, they are believed to play a role in regulating the step-wise changes in gene expression patterns that occur during cell fate specification of multipotent stem cells. Here, we have studied whether terminal differentiation of C2C12 myoblasts is indeed controlled by lineage-specific changes in miRNA expression.
MicroRNA miR-378 promotes BMP2-induced osteogenic differentiation of mesenchymal progenitor cells.
Cell line
View SamplesGlucocorticoids control expression of a large number of genes after binding to the glucocorticoid receptor (GR). Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive.
Prednisolone-induced differential gene expression in mouse liver carrying wild type or a dimerization-defective glucocorticoid receptor.
Sex, Specimen part
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Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Specimen part, Compound
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Integrating factor analysis and a transgenic mouse model to reveal a peripheral blood predictor of breast tumors.
Specimen part
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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
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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.
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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
View SamplesFemale MMTV/c-MYC transgenic mice expressed the c-MYC proto-oncogene or a more stable point mutation variant (T58A) of the gene under the control of the hormone-responsive MMTV long terminal repeat (LTR) in an FVB/NJ background (Jackson Laboratories, Bar Harbor, ME). The hormones released during pregnancy and lactation have been shown to enhance expression of the oncogene. Thus, the mice were maintained in a continuous breeding program. Mice were monitored twice weekly for tumor development by palpation and tumors were measured twice weekly. Once the tumors reached 3cm3 the animals were sacrificed and tissue was obtained to confirm the tumors by histological analysis. As a control, female mice of the same age and background strain were maintained in the same facility and under the same breeding conditions as their transgenic counterparts.
Integrating factor analysis and a transgenic mouse model to reveal a peripheral blood predictor of breast tumors.
Specimen part
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