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GSE13106
Mus musculus
10 Downloadable Samples
Description
Phosphorylation and subsequent nuclear translocation of SMAD proteins determine the cellular response to activin. Here we identify a novel means by which activin signalling is regulated to enable developmental stage-specific SMAD gene transcription. In response to activin A, immature proliferating mouse Sertoli cells exhibit nuclear accumulation of SMAD3, but not SMAD2, although both proteins are phosphorylated. In post-mitotic differentiating cells, both SMAD2 and SMAD3 accumulate in the nucleus. Furthermore, immature Sertoli cells are sensitive to activin dosage; at higher concentrations maximal SMAD3 nuclear accumulation is observed, accompanied by a small, but significant, increase in nuclear SMAD2. Microarray analysis confirmed that differential SMAD utilization correlated with altered transcriptional outcomes and identified new activin target genes, Gja1 and Serpina5, which are known to be required for Sertoli cell development and male fertility. In immature Sertoli cells, genetic or transient knockdown of SMAD3 enhanced SMAD2 nuclear accumulation in response to activin, with increased Serpina5 mRNA levels associated with nuclear localized SMAD2. In transgenic mice with altered activin bioactivity that display male fertility phenotypes, testicular Gja1 and Serpina5 mRNA levels reflected altered in vivo activin levels. We conclude that regulated nuclear accumulation of phosphorylated SMAD2 is a novel determinant of developmentally regulated activin signalling.
Publication Title
Developmentally regulated SMAD2 and SMAD3 utilization directs activin signaling outcomes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
IL-1R-associated kinases (IRAKs) participate in Toll-like receptor (TLR) signal transduction. MALP-2 is a TLR2 ligand, and stimulation of macrophages with MALP-2 activates expression of various genes including proinflammatory cytokines.
Publication Title
Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Polarization of macrophages to M1 or M2 cells is important for mounting responses against bacterial and helminth infection respectively. Jumonji domain containing 3 (JMJD3), a histone 3 K27 demethylase, has been implicated in the activation of macrophages. Here we show that JMJD3 is essential for M2 macrophage polarization to helminth infection and chitin, though JMJD3 is dispensable for M1 responses. Furthermore, Jmjd3 is critical for proper bone marrow macrophage differentiation in a demethylase activity-dependent manner. Jmjd3 deficiency affected trimethylation of H3K27 in only a limited numbers of genes. Among them, we identified Irf4 as the target transcription factor critical for controlling M2 macrophage polarization. Collectively, these results show that JMJD3-mediated H3K27 demethylation is critical for regulating M2 macrophage development leading to anti-helminth host responses.
Publication Title
The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
Description
Treatment of DBA/2J mice with a combination of L-methionine and valproic acid significantly attenuated progressive hearing loss. We examined gene expression in the whole cochlea of the mice. This study was aimed to detect genes of which change in expression levels were associated with attenuation of progressive hearing loss in the mice.
Publication Title
Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
We employed GeneChip analysis to investigate the global gene expression profiles of neutrophils from BM
Publication Title
Neutrophil priming occurs in a sequential manner and can be visualized in living animals by monitoring IL-1β promoter activation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 72 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
Sample Metadata Fields
Age, Specimen part, Disease
View Samples- Mus musculus
- 39 Downloadable Samples
Description
Liver global gene expression patterns of 9 GNMT-knockout mice histopathologically determined to have non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) together with 10 MAT1A-knockout mice histopathologically determined to have steatosis and NASH. All these have their respective wild type patterns. These were analyzed to define signatures to study the pathogenesis of NAFLD-derived HCC, explore which subtypes of cancers can be investigated using mouse models and define a signature of HCC differential survival that can be used to characterize HCC subtypes of different survival derived from mixed etiologies.
Publication Title
Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
Sample Metadata Fields
Age, Specimen part, Disease
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Dmrt1 (doublesex and mab-3 related transcription factor 1) is a conserved transcriptional regulator of male differentiation required for testicular development in vertebrates. This study examines the result of conditional removal of Dmrt1 from Sertoli cells in P28 testis tissue.
Publication Title
DMRT1 prevents female reprogramming in the postnatal mammalian testis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The aim of this study was to examine the role of indigenous lactobacilli in the physiological development of the stomach in mice using microarray analysis. In lactobacilli-associated gnotobiotic mice, an increased expression of the genes related to the muscle system development, such as nebulin and troponin, was observed. On the other hand, the expression of the gastrin gene dramatically decreased. A microarray analysis of the stomachs infected with H. pylori also showed both the up-regulation of muscle cell genes and the down-regulation of gastrin genes.
Publication Title
Role of indigenous lactobacilli in gastrin-mediated acid production in the mouse stomach.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
Description
Aquaporin-11 (AQP11), a new member of the aquaporin family, is localized in the endoplasmic reticulum (ER). Aqp11/ mice neonatally suffer from polycystic kidneys derived from the proximal tubule. Its onset is proceeded by the vacuolization of ER. However, the mechanism for the formation of vacuoles and the development of cysts remain to be clarified. Here, we show that Aqp11/ mice and polycystic kidney disease animals share a common pathogenic mechanism of cyst formation.
Publication Title
Aquaporin-11 knockout mice and polycystic kidney disease animals share a common mechanism of cyst formation.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples