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GSE37019
Danio rerio
5 Downloadable Samples
Description
In the early zebrafish embryo, the developing genome profile can be interfered with by exposure to pentachlorophenol, and some specific sets of genes are up-regulated or down-regulated. We used microarrays to detail the global program of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.
Publication Title
Pentachlorophenol exposure causes Warburg-like effects in zebrafish embryos at gastrulation stage.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Neural crest defects lead to congenital heart disease involving outflow tract (OFT) malformation. Integrin-linked-Kinase (ILK) plays important roles in multiple cellular processes and embryogenesis. ILK is expressed in neural crest cells (NCC), but its role in NCC and OFT morphogenesis remains unknown.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
While the functional roles of long non-coding RNAs (lncRNAs) have been increasingly identified, few lncRNAs that control the naive state of embryonic stem cells (ESCs) are known. Here, we report a naive-state-associated lncRNA, lincU, which is intrinsically activated by NANOG in naive mESCs. LincU-deficient mESCs exhibit a primed-like pluripotent state and potentiate the transition from naive state to primed state, whereas ectopic lincU expression maintains mESCs in the naive state. Mechanistically, we demonstrate that lincU directly binds and stabilizes the DUSP9 protein, an ERK-specific phosphatase, and then constitutively inhibits the ERK1/2 signaling pathway, which critically contributes to maintenance of the naive state. Importantly, we reveal the functional role of lincU to be evolutionarily conserved in human. Our findings thus unveil lincU as a conserved lncRNA that intrinsically restricts MAPK/ERK activity and maintains the naive state of ESCs.
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Sin3a, a known master scaffold, provides unique contact surfaces for interaction with particular accessory proteins to repress the transcription of specific genes. Surprisingly, our results also suggest that Sin3a has a role in transcriptional activation.
Publication Title
Sin3a-Tet1 interaction activates gene transcription and is required for embryonic stem cell pluripotency.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Little is known about the roles of methyl-CpG-binding domain protein 2 (MBD2), a reader of DNA methylation, in T-cell acute lymphoblastic leukemia (T-ALL). Here, we investigated the role of MBD2 in T-ALL by using an Mbd2 knockout mouse model. We found that MBD2 ablation impeded the progression and maintenance of Notch1-driven T-ALL.Our data reveals essential roles for MBD2 in lymphopoiesis and T-ALL and support an intriguing potential of MBD2 as a therapeutic target for T-ALL.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 54 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Sample Metadata Fields
Specimen part, Compound
View Samples- Mus musculus, Homo sapiens
- 94 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrating factor analysis and a transgenic mouse model to reveal a peripheral blood predictor of breast tumors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 231 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.
Sample Metadata Fields
Sex, Age, Disease stage, Race
View Samples- Mus musculus
- 54 Downloadable Samples
Description
The 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.
Publication Title
Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Sample Metadata Fields
Specimen part, Compound
View Samples