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GSE63638
Mus musculus
19 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
IDH2 and NPM1 Mutations Cooperate to Activate Hoxa9/Meis1 and Hypoxia Pathways in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mutations in IDH1 and IDH2 are frequently observed in various cancers, including acute myeloid leukemia (AML). Mutant IDHs convert -ketoglutarate (-KG) to 2-hydroxyglutarate (2-HG), which dysregulates a set of-KG-dependent dioxygenases. To determine whether mutant IDHs are valid targets for cancer therapy, we established a mouse AML model harboring an IDH2 mutation by transplanting mice with nucleophosmin1 (NPM1)+/- mouse hematopoietic stem/progenitor cells that had been co-transduced with four mutant genes (NPMc, IDH2/R140Q, DNMT3A/R882H and FLT3/ITD) that frequently occur simultaneously in human AML patients. IDH2/R140Q is necessary for the engraftment or survival of NPMc+ cells in vivo.Gene-expression analysis indicated that NPMc increased the expression of Hoxa9, and that IDH2/R140Q increased the level of Meis1 and activated the hypoxia pathway in AML cells.Conditional deletion of IDH2/R140Q blocked 2-HG production and maintenance of leukemia stem cells, resulting in survival of the AML mice. IDH2/R140Q reversibly decreased the levels of 5hmC modification and gene expression at some differentiation inducing genes (Ebf1, Pax5 and Spib). These results indicate that the IDH2 mutation is critical for the development and maintenance of AML stem cells, and that mutant IDHs are promising targets for anticancer therapy.
Publication Title
IDH2 and NPM1 Mutations Cooperate to Activate Hoxa9/Meis1 and Hypoxia Pathways in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 257 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BACKGROUND & AIMS: Metabolic syndrome is a newly identified risk factor for hepatocellular carcinoma (HCC), however the molecular mechanisms still remain unclear. To elucidate this issue, cross-species analysis was performed to compare gene expression patterns of HCC from human patients and melanocortin 4 receptor-knockout (MC4R-KO) mice, developing HCC with obesity, insulin resistance and dyslipidemia. METHODS: Unsupervised hierarchical clustering and principle component analysis of 746 differentially expressed orthologous genes classified HCC of 152 human patients and MC4R-KO mice into two distinct subgroups, one of which included all the mouse HCC was etiologically associated with metabolic risk factors, such as obesity and diabetes. A specific biomarker was identified by the integrative analysis, and validated with in vitro studies and other cohort patients. RESULTS: As commonly overexpressed in human and mouse metabolic disease-associated HCC, FABP4 was remarkably enriched in intratumoral activated hepatic stellate cells (HSCs). Then, we established subclones constitutively expressing FABP4 from a human HSC cell line, in which the expression levels of inflammatory chemokines including IL1A and IL6 was upregulated through NF-B nuclear translocation. An immunohistochemical validation study of other 106 human HCC samples indicated that FABP4-positive HSCs were distributed in tumors of 38 cases, and that the FABP4-high group was composed of patients with non-viral and non-alcoholic HCC (P=0.027) and with multiple metabolic risk factors (P<0.001) compared with the FABP4-low. CONCLUSIONS: FABP4 overexpression in HSCs could contribute to hepatocellular carcinogenesis in patients with metabolic risk factors via modulation of inflammatory pathway, and is a promising novel biomarker as well as a potential therapeutic target for this subtype of HCC.
Publication Title
Fatty Acid Binding Protein 4 (FABP4) Overexpression in Intratumoral Hepatic Stellate Cells within Hepatocellular Carcinoma with Metabolic Risk Factors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BACKGROUND & AIMS: Metabolic syndrome is a newly identified risk factor for hepatocellular carcinoma (HCC), however the molecular mechanisms still remain unclear. To elucidate this issue, cross-species analysis was performed to compare gene expression patterns of HCC from human patients and melanocortin 4 receptor-knockout (MC4R-KO) mice, developing HCC with obesity, insulin resistance and dyslipidemia. METHODS: Unsupervised hierarchical clustering and principle component analysis of 746 differentially expressed orthologous genes classified HCC of 152 human patients and MC4R-KO mice into two distinct subgroups, one of which included all the mouse HCC was etiologically associated with metabolic risk factors, such as obesity and diabetes. A specific biomarker was identified by the integrative analysis, and validated with in vitro studies and other cohort patients. RESULTS: As commonly overexpressed in human and mouse metabolic disease-associated HCC, FABP4 was remarkably enriched in intratumoral activated hepatic stellate cells (HSCs). Then, we established subclones constitutively expressing FABP4 from a human HSC cell line, in which the expression levels of inflammatory chemokines including IL1A and IL6 was upregulated through NF-B nuclear translocation. An immunohistochemical validation study of other 106 human HCC samples indicated that FABP4-positive HSCs were distributed in tumors of 38 cases, and that the FABP4-high group was composed of patients with non-viral and non-alcoholic HCC (P=0.027) and with multiple metabolic risk factors (P<0.001) compared with the FABP4-low. CONCLUSIONS: FABP4 overexpression in HSCs could contribute to hepatocellular carcinogenesis in patients with metabolic risk factors via modulation of inflammatory pathway, and is a promising novel biomarker as well as a potential therapeutic target for this subtype of HCC.
Publication Title
Fatty Acid Binding Protein 4 (FABP4) Overexpression in Intratumoral Hepatic Stellate Cells within Hepatocellular Carcinoma with Metabolic Risk Factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Keeping imbibed seeds at low temperatures for a certain period, so called seed vernalization (SV) treatment, promotes seed germination and subsequent flowering in various plants. Vernalization-promoting flowering requires GSH. However, the expression patterns analyzed by GeneChip arrays showed that increased GSH biosynthesis partially mimics SV treatment in Arabidopsis thaliana. SV treatment (keeping imbibed seeds at 4C for 24 h) induced a specific pattern of gene expression and promoted subsequent flowering in wild-type plants. A similar pattern was observed at 22C in transgenic plants (35S-GSH1 plants) overexpressing the -glutamylcysteine synthetase gene GSH1, coding an enzyme limiting GSH biosynthesis, under the control of the cauliflower mosaic virus 35S promoter. This pattern was strengthened at 4C but flowering was less responsive to SV treatment. There was a difference in the transcript behaviour of the flowering repressor FLC between wild-type and 35S-GSH1 plants. Unlike other genes responsive to SV treatment, SV-dependent decrease in FLC in wild-type plants was reversed in 35S-GSH1 plants. SV treatment increased GSSG level in wild-type seeds, whereas GSSG level was high in 35S-GSH1 plants, even at a non-vernalizing temperature. Taking into consideration that low temperatures stimulate GSH biosynthesis and bring about oxidative stress, GSSG is considered to trigger low temperature response, but enhanced GSH synthesis was not enough for mimicking SV treatment. To complete it, it essentially required the cellular redox retransition from the oxidized to the reduced state that is observed after the seed vernalization treatment.
Publication Title
Overexpression of GSH1 gene mimics transcriptional response to low temperature during seed vernalization treatment of Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Ras dexamethasone-induced protein 1 is a modulator of hormone secretion in the volume overloaded heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Pharmacological and gene ablation studies have demonstrated a crucial role of the caridac natriuretic peptides (NP) hormones ANF and BNP in the maintenance of cardiovascular homeostasis. Considerable effort has been focused on the elucidation of the mechanistic underlying increased atrial ANF and BNP expression and secretion. These investigations are important because under chronic congestive heart failure, the secretion of NPs although increased and beneficial, is relatively insufficient as demonstrated by the fact that patients benefit form the unloading of the heart induced by therapeutic administration of either ANF or BNP.
Publication Title
Ras dexamethasone-induced protein 1 is a modulator of hormone secretion in the volume overloaded heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Pharmacological and gene ablation studies have demonstrated a crucial role of the caridac natriuretic peptides (NP) hormones ANF and BNP in the maintenance of cardiovascular homeostasis. Considerable effort has been focused on the elucidation of the mechanistic underlying increased atrial ANF and BNP expression and secretion. These investigations are important because under chronic congestive heart failure, the secretion of NPs although increased and beneficial, is relatively insufficient as demonstrated by the fact that patients benefit form the unloading of the heart induced by therapeutic administration of either ANF or BNP.
Publication Title
Ras dexamethasone-induced protein 1 is a modulator of hormone secretion in the volume overloaded heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
There are a few markers for embryonic hepatic stellate cells in mouse embryonic livers
Publication Title
Isolation of a unique hepatic stellate cell population expressing integrin α8 from embryonic mouse livers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In the present study we investigate the role of IL-4 receptor a subunit in intestinal inflammation using DSS-induced colitis model. Our finding suggest that IL-4Ra deficiency enhances intestinal mucosal barrier function through the upregulation of NOX1-dependent ROS production, thereby suppressing the development of intestinal inflammation.
Publication Title
Interleukin-4 Receptor α Subunit Deficiency Alleviates Murine Intestinal Inflammation In Vivo Through the Enhancement of Intestinal Mucosal Barrier Function.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples