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GSE45702
Mus musculus
1 Downloadable Sample
Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
S-adenosylmethionine levels regulate the schwann cell DNA methylome.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseWG-6 v2.0 expression beadchip
Description
DNA methylation is a key epigenetic regulator of mammalian embryogenesis and somatic cell differentiation. Using high-resolution genome-scale maps of methylation patterns, we show that the formation of myelin in the peripheral nervous system, proceeds with progressive DNA demethylation, which coincides with an upregulation of critical genes of the myelination process. More importantly, we found that, in addition to expression of DNA methyltransferases and demethylases, the levels of S-adenosylmethionine (SAMe), the principal biological methyl donor, could also play a critical role in regulating DNA methylation during myelination and in the pathogenesis of diabetic neuropathy. In summary, this study provides compelling evidence that SAMe levels need to be tightly controlled to prevent aberrant DNA methylation patterns, and together with recently published studies on the influence of SAMe on histone methylation in cancer and embryonic stem cell differentiation show that in diverse biological processes, the methylome, and consequently gene expression patterns, are critically dependent on levels of SAMe.
Publication Title
S-adenosylmethionine levels regulate the schwann cell DNA methylome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Uncontrolled Transforming growth factor-beta (TGF) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGF-mediated cues are directed to induce late-stage tumorigenic events is poorly understood, particularly given that TGF has clear tumor suppressing activity in other contexts. Here we demonstrate that the transcriptional regulators TAZ and YAP (TAZ/YAP), key effectors of the Hippo pathway, are necessary to promote and maintain TGF-induced tumorigenic phenotypes in breast cancer cells. Interactions between TAZ/YAP, TGF-activated SMAD2/3, and TEAD transcription factors reveal convergent roles for these factors in the nucleus. Genome-wide expression analyses indicate that TAZ/YAP, TEADs and TGF-induced signals coordinate a specific pro-tumorigenic transcriptional program. Importantly, genes cooperatively regulated by TAZ/YAP, TEAD, and TGF, such as the novel targets NEGR1 and UCA1, are necessary for maintaining tumorigenic activity in metastatic breast cancer cells. Nuclear TAZ/YAP also cooperate with TGF signaling to promote phenotypic and transcriptional changes in non-tumorigenic cells to overcome TGF repressive effects. Our work thus identifies crosstalk between nuclear TAZ/YAP and TGF signaling in breast cancer cells, revealing novel insight into late-stage disease-driving mechanisms.
Publication Title
The transcriptional regulators TAZ and YAP direct transforming growth factor β-induced tumorigenic phenotypes in breast cancer cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Lhx5 controls mamillary differentiation in the developing hypothalamus of the mouse.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Lhx5 mutant mouse embryos show loss of a neuronal nucleus of the brain called the mamillary body and essential for the formation of memories. We wanted to identify the genes that are responsible for the normal development of the mammillary body.
Publication Title
Lhx5 controls mamillary differentiation in the developing hypothalamus of the mouse.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 52 Downloadable Samples
Illumina HiScanSQ
Description
Background & Aims. Glycine N-methyltransferase (GNMT) is an essential regulator of the total transmethylation flux in the mammalian liver. Distinct DNA methylation patterns are characteristic of liver development, hepatic de-differentiation and liver disease progression, processes in which the levels of GNMT decrease dramatically by mechanisms still poorly understood. Interestingly, putative binding sites for the microRNA miRNA-873-5p were identified in the 3´UTR of GNMT suggesting a potential role for miRNA-873-5p in GNMT regulation. Results. We have identified that the hepatic expression of miRNA-873-5p was increased in a cohort of cirrhotic and liver cancer patients associated with a down-regulation of GNMT levels. Moreover, during liver development, hepatic de-differentiation and fibrosis, the elevation of miRNA-873-5p coincided with the reduction of GNMT expression, indicating that miRNA-873-5p specifically targets the expression of GNMT. Under these circumstances, inhibition of miRNA-873-5p induced GNMT levels and decreased global CpG methylation and transmethylation flux. Indeed, reestablishment of GNMT expression by miRNA-873-5p inhibition reduced hepatocyte de-differentiation, and abolished completely the mortality produced after bile duct ligation as a result of decreased proinflamatory and profibrogenic markers. miRNA-873-5p knockdown-mediated antifibrotic effect was significantly blunted if its effect on GNMT was blocked. Conclusion. Taken together, our studies highlight the role of miRNA-873-5p as a key regulator of GNMT expression, paving the way for new therapeutical approaches in liver de-differentiation and fibrosis. Overall design: Genome-wide changes in gene Expression in mouse livers from BDL treated or not with anti-miR-873 were generated by RNAseq.
Publication Title
MiR-873-5p acts as an epigenetic regulator in early stages of liver fibrosis and cirrhosis.
Sample Metadata Fields
Age, Cell line, Treatment, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Different mutations in the gene encoding humans IGF-I cause intrauterine growth retardation, postnatal growth failure, microcephaly, mental retardation, bilateral sensorineural deafness and multiple dysmorphic features. Insight into the role of IGFs in inner ear cochlear ganglion neurogenesis has come from the study of genetically modified mice. Postnatal cochlear development is severely impaired in mice Igf1-/-, which develop smaller cochlea and cochlear ganglia, an immature tectorial membrane and they display a significant decrease in the number and size of auditory neurons.
Publication Title
RNA microarray analysis in prenatal mouse cochlea reveals novel IGF-I target genes: implication of MEF2 and FOXM1 transcription factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Methionine adenosyltransferase (MAT) enzymes generate SAMe (S-adenosylmethionine), the main biological methyl donor. There are two MAT encoding genes in mammals (Mat1a and Mat2a), which show different activities and cellular distribution. Mat1a encodes the enzyme mainly expressed in normal liver. Mat1a ablation in mice results in the spontaneous development of non-alcoholic steatohepatitis (NASH). We observed that SAMe depletion in Mat1a KO mice had three main effects on hepatic lipid metabolism: 1) impaired TG (triglyceride) export via VLDL; 2) impaired mitochondrial FA (fatty acid) oxidation (as evidenced by membrane depolarization, downregulation of Phb1 (prohibitin 1, a mitochondrial chaperone protein) and Mcj/Dnajc15 (endogenous mitochondrial repressor of respiratory chain), and accumulation of long-chain acylcarnitines); and 3) increased FA uptake. The convergence of these three factors induced TG accumulation in LD (lipid droplets). LD expansion confronts hepatocytes with a high demand of PC (phosphatidylcholine) molecules to cover the LD surface since other phospholipids, such as PE (phosphatidylethanolamine), cannot stabilize LD and prevent coalescence. In Mat1a KO this situation is aggravated, since SAMe-dependent PC synthesis via PE methylation is decreased, the PC/PE ratio reduced and mitochondrial FA oxidation impaired. To put a brake to this drain of PC molecules to LD, FA are rerouted in Mat1a KO mice liver to other catabolic (endoplasmic reticulum and peroxisome oxidation) and biosynthetic (ceramides synthesis) pathways, causing oxidative stress, inflammation and fibrosis. SAMe treatment for two months in 8-9 month old Mat1a KO mice ameliorated mitochondrial dysfunction (reduces membrane depolarization, improves Phb1 and Mcj expression, and increases SAMe transport to mitochondria) improving FA oxidation efficiency (FA and acylcarnitine levels decrease), which results in a drastic reduction in TG accumulation. SAMe treatment in Mat1a KO mice resulted in more PC available for proper membrane function, improving liver lipid homeostasis, histology (H&E, Sudan red, Sirius red) and liver injury (ALT, AST).
Publication Title
Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Insulin like growth factor 1 (IGF-1) has a central role in mammalian hearing and hearing loss. The auditory and vestibular systems form the inner ear and have a common developmental origin. During chicken early development IGF-1 modulates neurogenesis of the cochleovestibular ganglion but no further studies have been conducted to explore the potential role of IGF-1 in the vestibular system.
Publication Title
Comparative gene expression study of the vestibular organ of the Igf1 deficient mouse using whole-transcript arrays.
Sample Metadata Fields
Specimen part
View Samples