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GSE60747
Mus musculus
4 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
We used an in vitro cardiomyocyte differentiation system with inducible Hey1 or Hey2 expression to study target gene regulation in cardiomyocytes (CM) generated from murine embryonic stem cells (ESC). The effects of Hey1 and Hey2 are largely redundant, but cell type specific. The number of regulated genes is comparable between ESC and CM, but the total number of binding sites is much higher, especially in ESC, targeting mainly genes involved in transcriptional regulation and developmental processes. Repression by Hey generally correlates with the extent of Hey-binding to target promoters, subsequent Hdac recruitment and lower histone acetylation. Functionally, treatment with the Hdac inhibitor TSA abolished Hey target gene regulation. However, in CM the repressive effect of Hey-binding is lost for a subset of genes. These lack Hey-dependent histone deacetylation in CM and are enriched for binding sites of cardiac specific activators like Srf, Nkx2-5, and Gata4.
Publication Title
Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
Description
Triggering of B cell receptors (BCR) induces a massive synthesis of NFATc1 in splenic B cells. By inactivating the Nfatc1 gene and re-expressing NFATc1 we show that NFATc1 levels are critical for the survival of splenic B cells upon BCR stimulation. NFATc1 ablation led to decreased BCR-induced Ca++ flux and proliferation of splenic B cells, increased apoptosis and suppressed germinal centre formation and immunoglobulin class switch by T cell-independent antigens. By controlling IL-10 synthesis in B cells, NFATc1 supported the proliferation and IL-2 synthesis of T cells in vitro and appeared to contribute to the mild clinical course of Experimental Autoimmune Encephalomyelitis in mice bearing NFATc1-/- B cells. These data indicate NFATc1 as a key factor controlling B cell function.
Publication Title
NFATc1 affects mouse splenic B cell function by controlling the calcineurin--NFAT signaling network.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
Description
Rationale: Estrogens attenuate cardiac hypertrophy and increase cardiac contractility via their cognate receptors ER and ER. Since female sex hormones enhance global glucose utilization and because myocardial function and mass are tightly linked to cardiac glucose metabolism we tested the hypothesis that expression and activation of the estrogen receptor (ER) might be required and sufficient to maintain physiological cardiac glucose uptake in the murine heart. Methods and Results: Cardiac glucose uptake quantified in vivo by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was strongly impaired in ovarectomized compared to gonadal intact female C57BL/6JO mice. The selective ER agonist 16-LE2 and the non-selective ER and ER agonist 17-estradiol completely restored cardiac glucose uptake in ovarectomized mice. Cardiac FDG uptake was strongly decreased in female ER knockout mice (ERKO) compared to wild type littermates. Biochemical assays, affymetrix cDNA array analysis, western blotting and immuno-staining of cardiac glucose transporters revealed a positive correlation of ER dependent cardiac FDG uptake with preserved cardiac glucose transporter-1 expression and micro-vascular localization. Conclusions: Systemic activation of the ER estrogen receptor is sufficient and its expression is required to maintain physiological glucose uptake in the murine heart, which is likely to contribute to known cardio-protective estrogen effects.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
prenatal stress response, genetic modification
Publication Title
Differential effects of prenatal stress in 5-Htt deficient mice: towards molecular mechanisms of gene × environment interactions.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Genome-wide comparative gene expression analysis of callus tissue of osteoporotic mice (Col1a1-Krm2 and Lrp5-/-) and wild-type were performed to identify candidate genes that might be responsible for the impaired fracture healing observed in Col1a1-Krm2 and Lrp5-/- mice.
Publication Title
Osteoblast-specific Krm2 overexpression and Lrp5 deficiency have different effects on fracture healing in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
Background
Publication Title
Similar inflammatory DC maturation signatures induced by TNF or Trypanosoma brucei antigens instruct default Th2-cell responses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Although ischemic cardiomyopathy (ICM) is the leading cause of chronic heart failure, one of the most common diseases overall, many aspects of the molecular pathogenesis of ICM still remain to be clarified. It has been We have previously shown that the neural cell adhesion molecule (NCAM1, CD56) is upregulated in ischemic cardiomyopathy by novel isoforms of the transcription factor RUNX1 (AML1) and, in the current study, we show that this upregulation is attributed exclusively to the NCAM1 isoform CD56-140kD. Moreover, we show that the upregulation of CD56-140kD has proapoptotic and antiproliferative effects on cardiomyocytes in vitro as well as inducing mitochondrial damage and reducing the capacity for Ca2+-uptake. As loss of cells and negative inotropy have previously been identified as major components in the development of ischemic cardiomyopathy, these data suggest that the upregulation of CD56-140kD may play a relevant role in the pathogenesis of ICM and therapeutic strategies targeting this molecule may prove to be valuable tools in the management of this very common and often fatal disease in the future.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Activation of oncogene signaling in primary cells generally results in cellular senescence. This process is not only considered to be tumor-protective, but also irreversible. However, if senescence induction can be circumvented, e.g. by additional genetic or epigenetic changes, tumor progression occurs. An in-vivo example for oncogene-induced senescence are human nevus cells, most of which bear oncogenic mutations in RAS/RAF/MAPK pathway genes. Here, we show that expression of the human melanoma oncogene N-RAS61K in cultured pigment cells initially induces OIS characterized by a highly multinucleated phenotype. Surprisingly, after prolonged periods of oncogene expression, mononucleated cells emerge from the multinucleated cells. They are highly proliferative, anoikis-resistent and induce fast growing and metastatic melanoma upon transplantation into nude mice. During long-term oncogene expression and the corresponding development of anoikis iresistance, expression of melanocyte-specific genes is lost. Our data demonstrate that the induction of oncogene-induced senescence is not just a failsafe escape mechanism, but also provides a source for highly aggressive tumor cells.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Description
The development of malignant melanoma is a highly complex process which is still poorly understood despite extensive research. A majority of human melanomas are found to express a handful of oncogenic proteins, such as mutant RAS and BRAF. However, these oncogenes are also found in nevi, and it is now a well-accepted fact that their expression alone leads to senescence. This renders the understanding of senescence escape mechanisms an important criterion to understand tumor development. Here, we describe the ability of the transcription factor MYC to drive the evasion of reactive oxygen stress-induced melanocyte senescence, caused by activated receptor tyrosine kinase signaling. Conversely, MIZ1, the growth suppressing interaction partner of MYC, is involved in mediating melanocyte senescence. Both, MYC overexpression and Miz1 knockdown led to a strong reduction of endogenous reactive oxygen species (ROS), DNA damage and senescence. We identified the cystathionase (CTH) gene product as mediator of the ROS-related MYC and MIZ1 effects. Blocking CTH enzymatic activity in MYC-overexpressing and Miz1 knockdown cells increased intracellular stress and senescence. Importantly, pharmacological inhibition of cystathionase in human melanoma cells also reconstituted senescence in many cell lines, and CTH knockdown reduced tumorigenic effects such as proliferation, H2O2 resistance and soft agar growth. Thus, we identified cystathionase as new MYC target gene with an important function in MYC-mediated senescence evasion.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
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