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Mus musculus
16 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease and a leading cause of liver transplantation in the United Sates. Hedgehog (Hh) signaling has been implicated in liver lipid metabolism and the early stages of NAFLD; however, its precise role remains unclear. We examined the prevalence of NAFLD in patients with overt or microform holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Hh signaling. To test the hypothesis that Hh signaling attenuation predisposes to liver steatosis, we subjected Gli2 heterozygous null (Gli2+/-) mice to two unique dietary models of fatty liver. Compared to the general population, the prevalence of NAFLD was significantly higher in the HPE cohort independent of obesity, especially among younger individuals. Gli2 heterozygosity caused increased weight gain and liver steatosis on a high fat diet, and increased liver steatosis in the absence of weight gain on a methionine and choline deficient diet. Increased liver steatosis in Gli2+/- mice was associated with decreased expression of pro-fibrotic and pro-inflammatory genes and increased expression of PPAR, a potent anti-fibrogenic and anti-inflammatory regulator. In addition, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2+/- mice. Our results indicate that germline mutations affecting Hh signaling predispose to NAFLD with reduced or absent fibrosis, and might increase the risk of hepatocellular carcinoma.
Publication Title
Human germline hedgehog pathway mutations predispose to fatty liver.
Sample Metadata Fields
Specimen part
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GSE56810- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The interior of the eukaryotic cell nucleus is a highly organized 3D structure. In mature hippocampal and cortical pyramidal neurons, transcriptionally silent DNA is typically compacted in a few clusters referred to as chromocenters that are strongly stained with DNA intercalating agents like DAPI and whose function is still uncertain. We found that this 3D structure was severely disrupted by the incorporation of the chimeric histone H2BGFP into neuronal chromatin. Experiments in inducible and forebrain restricted bitransgenic mice demonstrated that the expression of this histone alters the higher-order organization of neuronal heterochromatin and causes a complex behavioral phenotype that includes hyperactivity, and social interaction, prepulse inhibition and cognitive defects. This phenotype was associated with highly specific transcriptional deficits that affected several serotonin receptor genes located at the edge of gene desert regions. Pharmacological and electrophysiological experiments indicate that this epigenetically-induced hyposerotonergic state may underlie the behavioral defects. Our results suggest a new role for perinuclear heterochromatin and chromocenter organization in the epigenetic regulation of neuronal gene expression and mental illness.
Publication Title
Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
NOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide (MDP) and variants of NOD2 are associated with chronic inflammatory diseases of barrier organs e.g. Crohn disease, asthma and atopic eczema. It is known that activation of NOD2 induces a variety of inflammatory and antibacterial factors. The exact transcriptomal signatures that define the cellular programs downstream of NOD2 activation and the influence of the Crohn-associated variant L1007fsinsC are yet to be defined. To describe the MDP-induced activation program, we analyzed the transcriptomal reactions of isogenic HEK293 cells expressing NOD2wt or NOD2L1007fsinsC to stimulation with MDP. Importantly, a clear loss-of-function could be observed in the cells carrying the Crohn-associated variant L1007fsinsC, while the NOD2wt cells showed differential regulation of growth factors, chemokines and several antagonists of NF-B, e.g. TNFAIP3 (A20) and IER3.
Publication Title
Genome-wide expression profiling identifies an impairment of negative feedback signals in the Crohn's disease-associated NOD2 variant L1007fsinsC.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 3000
Description
A coding variant of the inflammatory bowel disease (IBD) risk gene ATG16L1 has been associated with defective autophagy and deregulation of endoplasmic reticulum (ER) function. IL-22 is a barrier protective cytokine by inducing regeneration and antimicrobial responses in the intestinal mucosa. We show that ATG16L1 critically orchestrates IL-22 signaling in the intestinal epithelium. IL-22 stimulation physiologically leads to transient ER stress and subsequent activation of STING dependent type I interferon (IFN-I) signaling, which is augmented in Atg16l1?IEC intestinal organoids. IFN-I signals amplify epithelial TNF production downstream of IL-22 and contribute to necroptotic cell death. In vivo, IL-22 treatment in Atg16l1?IEC and Atg16l1?IEC/Xbp1?IEC mice potentiates endogenous ileal inflammation and causes widespread necroptotic epithelial cell death. Therapeutic blockade of IFN-I signaling ameliorates IL-22 induced ileal inflammation in Atg16l1?IEC mice. Our data demonstrate an unexpected role of ATG16L1 in coordinating the outcome of IL-22 signaling in the intestinal epithelium. Overall design: Organoids from Atg16l intestinal knockout vs. Wildtype
Publication Title
ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS-STING.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 69 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Microarray analysis revealed that changes in genes expressions are brain region-dependent; expression of several genes are affected by point mutation L100P, which was verified by RT-PCR (Lcn2, Cyr61, Slc6a12, Slc40a1, Egr2), a few genes are affected by genotype and valproate (Dusp1 and Purb), suggesting their role in valproate-induced benificial effect on sensorimotor gaiting in Disc1-L100P mutant mice. The final conclusion will be drawn after series of RT-PCR confirmation.
Publication Title
Genetic and pharmacological evidence for schizophrenia-related Disc1 interaction with GSK-3.
Sample Metadata Fields
Sex, Specimen part, Compound
View Samples GSE75789- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with extremely low median survival rate of 12-15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to such treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and -5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased of cell proliferation, and increased cell cycle arrest and apoptosis in comparison to only irradiated cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation and cell cycle regulation. To our knowledge, this is the first study to describe role of miR-338-5p in GBM and its potential to improve sensitivity of GBM to radiation.
Publication Title
MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
CD25+ regulatory T cells develop in the thymus (nTregs), but may also be generated in the periphery upon stimulation of naive CD4 T cells under appropriate conditions (iTregs). The mechanisms that regulate the generation of peripheral iTregs are largely unknown.
Publication Title
Analysis of the transcriptional program of developing induced regulatory T cells.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
In this experiment, total RNA was extracted from asynchronous population of L1210 cells and hybridized to Affymetrix 430A 2.0 arrays in order to obtain an expression profile of these cells. We have previously mapped the replication timing of the entire mouse genome in this cell line, using mouse CGH arrays (see E-MEXP-1022). We wanted to validate in our system the known correlation between early replication and expression and to analyze its extent. To this end, we have measured the expression in the same cell line (L1210 cells). Two biological replicates were hybridized to 2 identical microarrays. Expression levels were highly similar between the 2 replicates (r=0.98).
Publication Title
Global organization of replication time zones of the mouse genome.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 44 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective Tissue Growth Factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. To test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase C (PKC) mouse model of DCM. Transgenic mice expressing constitutively active PKC in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to heart failure, cardiac fibrosis, and increased mortality. Beginning at 3 months of age, mice were treated with an antibody to CTGF (FG-3149) or non-immune IgG control antibody for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic function in PKC mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling were elevated in PKC mice, but significantly decreased by CTGF inhibition, however total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKC mice suggests that CTGF inhibition may benefit patients with DCM.
Publication Title
Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples