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GSE35471
Drosophila melanogaster
5 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Growth of the drosophila eye imaginal discs is controlled by the activation of Notch in the dorsal-ventral boundary. Overexpression in the eye disc of the Notch ligand Delta together with lola and pipsqueak from the GS(2)88A8 line induces tumoral growth. We used microarray to analyze the expression profile of tumoral discs.
Publication Title
Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Diamond-Blackfan Anemia (DBA) is a rare inherited red cell hypoplasia characterized by a defect in the maturation of erythroid progenitors and is in some cases associated to malformations. Patients have an increased risk of solid tumors. Mutations have been found in several ribosomal protein (RP) genes. Studies in hematopoietic progenitors from patients show that the haploinsufficiency of an RP impairs rRNA processing and ribosome biogenesis. DBA lymphocytes and fibroblasts show reduced protein synthesis, and the latter display abnormal rRNA processing and impaired proliferation.
Publication Title
Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer.
Sample Metadata Fields
Sex, Disease, Disease stage
View Samples- Mus musculus
- 9 Downloadable Samples
Illumina HiSeq 1500
Description
Purpose:This work aimed to identify the genetic profiles of piriform projection neurons and characterize their spatial organization within the piriform cortex. Methods: We microdissected the three layers of pirifrom cortex by laser capture (LMD) and performed RNA deep sequencing in order to identify layer-specific molecular markers, we then validated these data by using RNA in situ hybridization and immunohistochemistry.We next performed anterograde neural tracing experiments to identify piriform target regions, and retrograde neural tracing experiments to analyze how piriform projection neurons are organized within piriform cortex.We then combined the analysis of patterns of gene expression with retrograde tracing experiments to identify molecular signatures of the different subclasses of piriform projecting neurons. Results:We show that layers and sub-layers of the piriform cortex can be discriminated by gene expression patterns in adult piriform cortex. We observe that neurons projecting to distinct target areas are localized in distinct layers and express specific genes. We demonstrate that these molecular signatures of piriform projection neurons are maintained in reeler mice, in which cortical lamination is lost and neural positioning is scrambled, suggesting that piriform output connectivity strictly depends on the molecular programm, rather than a proper lamination of the cortex. Conclusion:These results provide important insights into the principles underling the piriform connectivity. Overall design: 3 replicates per each layer (three layers) of piriform cotrex were used for the RNA deep sequancing
Publication Title
Molecular signatures of neural connectivity in the olfactory cortex.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- NextSeq 500
Description
Background: Here, the role of a-ketoglutarate (aKG) in the epi-metabolic control of DNA demethylation has been investigated in therapeutically relevant cardiac mesenchymal cells (CMSCs) isolated from controls and type 2 diabetes donors. Methods & results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs). Whole heart genomic DNA analysis revealed iterative oxidative cytosine modification accumulation in mice exposed to high fat diet (HFD), injected with streptozotocin (STZ) or both in combination (STZ-HFD). In this context, untargeted and targeted metabolomics indicated an intracellular reduction of aKG synthesis in D-CMSCs and in the whole heart of HFD mice. This observation was paralleled by a compromised thymine DNA glycosylase (TDG) and ten eleven translocation protein 1 (TET1) association and function with TET1 relocating out of the nucleus. Molecular dynamics and mutational analyses showed that aKG binds TDG on Arg275 providing an enzymatic allosteric activation. As a consequence, the enzyme significantly increased its capacity to remove G/T nucleotide mismatched or 5fC. Accordingly, an exogenous source of aKG restored the DNA demethylation cycle by promoting TDG function, TET1 nuclear localization and TET/TDG association. TDG inactivation by CRISPR/Cas9 knockout or TET/TDG siRNA knockdown induced 5fC accumulation thus partially mimicking the diabetic epigenetic landscape in cells of non- diabetic origin. The novel compound (S)-2-[(2,6-dichlorobenzoyl)amino]succinic acid (AA6), identified as an inhibitor of aKG-dehydrogenase, increased the aKG level in D- CMSCs and in the heart of HFD mice eliciting DNA demethylation, glucose uptake and insulin response. Conclusions: In this report we established that diabetes may epigenetically modify and compromise function of therapeutically relevant cardiac mesenchymal cells. Restoring the epi-metabolic control of DNA demethylation cycle promises beneficial effects on cells compromised by environmental metabolic changes. Overall design: Human primary cardiac mesenchymal cells (CMSC) from 7 diabetic (D) and 7 non-diabetic (ND) donors were analyzed after few rounds of ex vivo expansion. RNA was isolated and sequenced.
Publication Title
Stable Oxidative Cytosine Modifications Accumulate in Cardiac Mesenchymal Cells From Type2 Diabetes Patients: Rescue by α-Ketoglutarate and TET-TDG Functional Reactivation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human umbilical cord Whartons jelly stem cells (WHJSC) are gaining attention as a possible clinical source of mesenchymal stem cells for use in cell therapy and tissue engineering due to their high accessibility, expansion potential and plasticity. However, the cell viability changes that are associated to sequential cell passage of these cells are not known. In this analysis, we have identified the gene expression changes that are associated to cell passage in WHJSC.
Publication Title
Evaluation of the cell viability of human Wharton's jelly stem cells for use in cell therapy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Compare the behaviour of two populations of non-hematopoetic stem cells (MSC and MAPC) isolated from human bone marrow. The effect of culture conditions on the behaviour of MSC was also characterised by isolating MSC and then culturing the cells for 96h in MAPC growth conditions
Publication Title
Validation of COL11A1/procollagen 11A1 expression in TGF-β1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Multiple myeloma (MM) remains incurable despite the introduction of novel agents and a relapsing course is observed in the majority of patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from 17 MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the lost of lesions present at diagnosis, and DNA losses were significantly more frequent at relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly impact the gene expression of these samples, provoking a particular deregulation of IL-8 pathway. On the contrary, no relevant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although different statistical approaches were used to uncover genes whose abnormal expression at relapse was regulated by DNA methylation, only two genes significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative methylation-expression correlation. A deeper analysis demonstrated that DNA methylation was involved in regulation of SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were not apparently preceded by alterations in corresponding DNA. Taken together, these results showed that genomic heterogeneity, both at the DNA and RNA level, is a hallmark of MM transition from diagnosis to relapse.
Publication Title
Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background: Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gaq-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gaq acts as an adaptor protein that facilitates PKCz-mediated activation of ERK5 in epithelial cells. Since the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in Gq-dependent signaling in cardiac cells.
Publication Title
Protein kinase C (PKC)ζ-mediated Gαq stimulation of ERK5 protein pathway in cardiomyocytes and cardiac fibroblasts.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
Members of the JNK pathway have been found to be mutated in human breast cancer. Mouse studies examining JNK loss in different tissues have demonstrated that the JNK pathway can play a role in cancer. Using and autochthonous mouse model, we found that JNK deficiency on a p53-null background resulted in more rapid tumor onset. To learn more about these tumors we generated cells lines and performed various in vitro assays, as well as RNAseq in hope of finding differentially expressed genes that may explain the differences we observed in vivo. Overall design: Tumors were harvested from mice and cells lines were established from them. RNA was isolated from established tumor cell lines.
Publication Title
The cJUN NH<sub>2</sub>-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation.
Sample Metadata Fields
Cell line, Subject
View Samples