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GSE5654
Mus musculus
6 Downloadable Samples
Description
Knockdown of the transcription factor PU.1 (Spi1) leads to acute myeloid leukemia (AML) in mice. We examined the transcriptome of PU.1 knockdown hematopoietic stem cells (HSC) in the preleukemic phase by linear amplification and genome-wide array analysis to identify transcriptional changes preceding malignant transformation. Hierarchical cluster analysis and principal component analysis clearly distinguished PU.1 knockdown from wildtype HSC. Jun family transcription factors c-Jun and JunB were among the top downregulated targets. Retroviral restoration of c-Jun expression in bone marrow cells of preleukemic mice partially rescued the PU.1-initiated myelomonocytic differentiation block. Lentiviral restoration of JunB at the leukemic stage led to reduced clonogenic growth, loss of leukemic self-renewal capacity, and prevented leukemia in transplanted NOD-SCID mice. Examination of 305 AML patients confirmed the correlation between PU.1 and JunB downregulation and suggests its relevance in human disease. These results delineate a transcriptional pattern that precedes the leukemic transformation in PU.1 knockdown HSC and demonstrate that decreased levels of c-Jun and JunB contribute to the development of PU.1-induced AML by blocking differentiation (c-Jun) and increasing self-renewal (JunB). Therefore, examination of disturbed gene expression in HSC can identify genes whose dysregulation is essential for leukemic stem cell function and are targets for therapeutic interventions.
Publication Title
Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Description
Quercetin is a food component that may ameliorate the diabetic symptoms. We examined hepatic gene expression of BALB/c mice with streptozotocin (STZ)-induced diabetes to elucidate the mechanism of the protective effect of dietary quercetin on diabetes-associated liver injury.
Publication Title
Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
Description
To determine the effect of consumption of a quercetin-rich diet on obesity and dysregulated hepatic gene expression, C56BL/6J mice were fed for 20 weeks on control or a Western diet high in fat, cholesterol and sucrose, both with or without 0.05% quercetin. Chronic dietary intake of quercetin reduced body weight gain and visceral and liver fat accumulation, and improved hyperglyceamia, hyperinsulinaemia, dyslipidaemia in mice fed a Western-style diet.
Publication Title
Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western-style diet in C57/BL6J mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
PTEN loss or PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, in preclinical murine models, deletion of Pten alone fails to mimic the significant metastatic burden that frequently accompanies the end stage of human disease. To identify additional pathway alterations that cooperate with PTEN loss in prostate cancer progression, we surveyed human prostate cancer tissue microarrays and found that the RAS/MAPK pathway is significantly elevated both in primary and metastatic lesions. In an attempt to model this event, we crossed conditional activatable K-rasG12D/WT mice with the prostate conditional Pten deletion model we previously generated. Although RAS activation alone cannot initiate prostate cancer development, it significantly accelerated progression caused by PTEN loss, accompanied by epithelial-to-mesenchymal transition (EMT) and macrometastasis with 100% penitence. A novel stem/progenitor subpopulation with mesenchymal characteristics was isolated from the compound mutant prostates, which was highly metastatic upon orthotopic transplantation. Importantly, inhibition of RAS/MAPK signaling by PD325901, a MEK inhibitor, significantly reduced the metastatic progression initiated from transplanted stem/progenitor cells. Collectively, these data indicate that activation of RAS/MAPK signaling serves as a potentiating second hit to alteration of the PTEN/PI3K/AKT axis and co-targeting both pathways is highly effective in preventing the development of metastatic prostate cancers.
Publication Title
Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
Description
genes regualted by LPS or LPS+cAMP stimulation in BMDCs
Publication Title
Cyclic adenosine monophosphate suppresses the transcription of proinflammatory cytokines via the phosphorylated c-Fos protein.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Waldenstom macroglobulinemia (WM) with 6q del is still unknown. In the present study, we analyzed gene expression signiture of WM with 6q del.
Publication Title
Gene Expression Profile Signature of Aggressive Waldenström Macroglobulinemia with Chromosome 6q Deletion.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 3 Downloadable Samples
Description
Microarray analysis of Myd88-/-Trif-/- and Myd88-/-Rip2-/- macrophage responses to WT or dotA mutant L. pneumophila.
Publication Title
Type IV secretion-dependent activation of host MAP kinases induces an increased proinflammatory cytokine response to Legionella pneumophila.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
Description
To elucidate the bioactive property of the dietary antioxidant curcumin, we examined tissue distribution and the gene expression- and lipidomic-profiles in epididymal white adipose tissue (eWAT) of the diet-induced obese mice. Dietary intake of curcumin (0.1% W/W) didnt affect the eWAT weight and the plasma lipid levels but reduced the levels of lipid peroxidation marker in eWAT. Curcumin was a slightly accumulated in eWAT and altered the gene expression associated with eukaryotic translation initiation factor 2 (EIF2) signaling. Curcumin suppressed the endoplasmic reticulum (ER) stress-related eIF2 phospholyration, the accumulation of macrophages and the expression of oxidative stress-sensitive transcription factor NF-B p65 and leptin, whereas anti-inflammatory effect wasnt enough to reduce the TNF- and IFN- levels. Lipidomic- and gene expression analysis suggests that curcumin reduced the contents of some diacylglyverols (DAGs) and DAG derived glycerophospholipids by suppressing the expressions of lipogenesis-related glycerol-3-phosphate acyltransferase 1 and lipolysis-related adipose triglyceride lipase.
Publication Title
Dietary Intake of Curcumin Improves eIF2 Signaling and Reduces Lipid Levels in the White Adipose Tissue of Obese Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
We compared the gene expressions of the intestine, liver and spleen tissues between mice at 4 months of age and mice at 28 months of age. We used microarrays to examine the age-related changes of gene expressions of the jejunum, ileum, distal colon, liver and spleen in mice. Abbreviations used: C, 28-month-old mice; Y, 4-month-old mice.
Publication Title
Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples