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GSE26816
Mus musculus
5 Downloadable Samples
Description
Ptf1a was identified as the essential transcription factor which controls pancreatic exocrine enzyme expression. With lineage tracing eperiments Ptf1a was recognized as an important pancreatic progenitor transcription factor and Ptf1a null mice do not develop a pancreas.
Publication Title
RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Interleukin 2 (IL-2), a cytokine linked to human autoimmune diseases, limits IL-17 production. We show that deletion of Stat3 in T cells abrogates IL-17 production and attenuates autoimmunity associated with IL-2 deficiency. While STAT3 induces IL-17 and RORt and inhibits Foxp3, IL-2 inhibited IL-17 independently of Foxp3 and RORt. We found that STAT3 and STAT5 bound to multiple common sites across the Il17 genetic locus. The induction of STAT5 binding by IL-2 was associated with a reduction in STAT3 binding at these sites and the inhibition of associated active epigenetic marks. Titrating the relative activation of STAT3 and STAT5 modulated TH17 cell specification. Thus, the balance rather than the absolute magnitude of these signals determines the propensity of cells to make a key inflammatory cytokine.
Publication Title
Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1-4. Crucial for T helper17 (Th17) cells in vivo5,6, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-1 have been argued to be the factors responsible for initiating specification7-10. Herein, we show that Th17 differentiation occurs in the absence of TGF- signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1 effectively induced IL-17 production in nave precursors, independently of TGF-. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-1, allowing the generation of cells that co-expressed Rort and T-bet. T-bet+Rort+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies.
Publication Title
Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The anti-diabetic drug and agonist of the peroxisome proliferator-activated receptor gamma (Pparg), rosiglitazone, was recently withdrawn in many countries because the drug use was associated with an increased risk of heart failure. To investigate underlying pathomechanisms, we chose 6-month-old apolipoprotein E (apoE)-deficient mice, which are prone to atherosclerosis and insulin resistance, and thereby mimic the risk profile of patients with cardiovascular disease. After 8 weeks of rosiglitazone treatment (30 mg/kg/day), echocardiography and histology analyses demonstrated that rosiglitazone had induced heart failure with cardiac dilation. Concomitantly, cardiac lipid overload and lipid-induced cardiomyocyte death developed. The microarray gene expression study of heart tissue from rosiglitazone-treated apoE-deficient mice relative to untreated apoE-deficient mice and non-transgenic B6 mice identified cardiac Pparg-dependent lipid metabolism genes in rosiglitazone-treated mice, which seem to trigger a major heart failure promoting pathway.
Publication Title
Inhibition of G-protein-coupled Receptor Kinase 2 Prevents the Dysfunctional Cardiac Substrate Metabolism in Fatty Acid Synthase Transgenic Mice.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genomic binding of PAX8-PPARG fusion protein regulates cancer-related pathways and alters the immune landscape of thyroid cancer.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
Description
PAX8-PPARG fusion protein (PPFP) results from a t(2;3)(q13;p25) chromosomal translocation, is found in 30% of follicular thyroid carcinomas, and demonstrates oncogenic capacity in transgenic mice. A PPARG ligand, pioglitazone, is highly therapeutic in mice with PPFP thyroid carcinoma. We used our previously characterized transgenic mouse model of PPFP thyroid carcinoma to identify PPFP binding sites in vivo using ChIP-seq, and to identify genes and pathways regulated by PPFP with and without pioglitazone treatment via integration with RNA-seq and Affymetrix microarray data. This submission contains the Affymetrix microarray data. PPFP and pioglitazone regulated genes involved in lipid and fatty acid metabolism, ribosome function, immune processes, cell death and other cancer-related processes. The RNA-seq data yielded similar findings.
Publication Title
Genomic binding of PAX8-PPARG fusion protein regulates cancer-related pathways and alters the immune landscape of thyroid cancer.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 1 Downloadable Sample
Description
POU4F1 is associated with t(8;21) acute myeloid leukemia (AML) and contributes directly to its unique transcriptional signature
Publication Title
POU4F1 is associated with t(8;21) acute myeloid leukemia and contributes directly to its unique transcriptional signature.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
Description
Toxin A (TcdA) and Toxin B (TcdB), of the pathogen Clostridium difficile, are virulence factors that cause gross pathologic changes (e.g. inflammation, secretion, and diarrhea) in the infected host, yet the molecular and cellular pathways leading to observed host responses are poorly understood. To address this gap, TcdA and/or TcdB were injected into the ceca of mice and the genome-wide transcriptional response of epithelial layer cells was examined. Bioinformatic analysis of gene expression identified sets of cooperatively expressed genes. Further analysis of inflammation associated genes revealed dynamic chemokine responses.
Publication Title
In vivo physiological and transcriptional profiling reveals host responses to Clostridium difficile toxin A and toxin B.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 27 Downloadable Samples
Description
We used a novel probe-level microarray analysis, revealing connections between mRNA processing and lymphoid neoplasia, in a mouse leukemia model. Characteristic differences in mRNA processing, primarily in the 3-untranslated region, distinguished histologically similar tumor subtypes with different survival characteristics. Gene sets with specific processing in each tumor subtype defined signatures useful for tumor subclassification, as demonstrated by internal cross-validation with up to 80% discrimination accuracy. A combination of mRNA expression and sequence analysis suggested that differences in isoform abundance likely arose from both alternative polyadenylation and differential degradation.
Publication Title
Global changes in processing of mRNA 3' untranslated regions characterize clinically distinct cancer subtypes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
Mouse infection with the tapeworm Hymenolepis diminuta leads to a less severe DNBS-colitis. Increased Th2 and regulatory cytokine production in the spleen is a hallmark of Hymenolepis diminuta infection, therefore we hypothesized that given this microenvironment, splenic adaptive cells acquire an anti-inflammatory phenotype. We tested the ability of putative splenic regulatory B cells generated by Hymenolepis diminuta infection to down-regulate intestinal inflammation. We found that unlike splenic B cells from uninfected mice, splenic B cells from Hymenolepis diminuta -infected animals ameliorated chemically-induced colitis.
Publication Title
Splenic B cells from Hymenolepis diminuta-infected mice ameliorate colitis independent of T cells and via cooperation with macrophages.
Sample Metadata Fields
Specimen part
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