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Mus musculus
18 Downloadable Samples
Illumina HiSeq 2000
Description
Tfh and B cells were cultured together with or without Tfr cells. After 4 days Tfh and B cells were sorted and prepared for 3'' targeted RNA-seq. Overall design: Examination of transcriptional changes upon suppression of Tfh and B cells.
Publication Title
Suppression by T<sub>FR</sub> cells leads to durable and selective inhibition of B cell effector function.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
Tfh and B cells were cultured together with or without Tfr cells and IL-21. After 4 days Tfh and B cells were sorted and prepared for 3'' targeted RNA-seq. Overall design: Examination of transcriptional changes upon IL-21 rescue of B cell suppression
Publication Title
Suppression by T<sub>FR</sub> cells leads to durable and selective inhibition of B cell effector function.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Subject
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GSE56321- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sirtuins are a family of protein deacetylases, deacylases, and ADP-ribosyltransferases that regulate life span, control the onset of numerous age-associated diseases, and mediate metabolic homeostasis. We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism during changes in nutrient availability. We show that SIRT4 levels decrease in the liver during fasting and that SIRT4 null mice display increased expression of hepatic peroxisome proliferator activated receptor (PPAR ) target genes associated with fatty acid catabolism. Accordingly, primary hepatocytes from SIRT4 knockout (KO) mice exhibit higher rates of fatty acid oxidation than wild-type hepatocytes, and SIRT4 overexpression decreases fatty acid oxidation rates. The enhanced fatty acid oxidation observed in SIRT4 KO hepatocytes requires functional SIRT1, demonstrating a clear cross talk between mitochondrial and nuclear sirtuins. Thus, SIRT4 is a new component of mitochondrial signaling in the liver and functions as an important regulator of lipid metabolism.
Publication Title
SIRT4 represses peroxisome proliferator-activated receptor α activity to suppress hepatic fat oxidation.
Alternate Accession IDs
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 108 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Contemporary treatment of pediatric acute myeloid leukemia (AML) requires the assignment of patients to specific risk groups. To explore whether expression profiling of leukemic blasts could accurately distinguish between the known risk groups of AML, we analyzed 130 pediatric and 20 adult AML diagnostic bone marrow or peripheral blood samples using the Affymetrix U133A microarray. Class discriminating genes were identified for each of the major prognostic subtypes of pediatric AML, including t(15;17)[PML-RARalpha], t(8;21)[AML1-ETO], inv(16) [CBFbeta-MYH11], MLL chimeric fusion genes, and cases classified as FAB-M7. When subsets of these genes were used in supervised learning algorithms, an overall classification accuracy of more than 93% was achieved. Moreover, we were able to use the expression signatures generated from the pediatric samples to accurately classify adult de novo AMLs with the same genetic lesions. The class discriminating genes also provided novel insights into the molecular pathobiology of these leukemias. Finally, using a combined pediatric data set of 130 AMLs and 137 acute lymphoblastic leukemias, we identified an expression signature for cases with MLL chimeric fusion genes irrespective of lineage. Surprisingly, AMLs containing partial tandem duplications of MLL failed to cluster with MLL chimeric fusion gene cases, suggesting a significant difference in their underlying mechanism of transformation. All the gene expression arrays are available through http://www.stjuderesearch.org/site/data/AML1/ in the original study (PMID:15226186). To study the RAS gene expression in the human AML patients, a total of 104 AML cases with known KRAS and NRAS status (including 72 gene expression arrays in the original study and 32 additional arrays acquired later on), as well as 4 CD34+ normal bone marrow cases deposited in GEO GSE33315, were including in this depository.
Publication Title
Dominant role of oncogene dosage and absence of tumor suppressor activity in Nras-driven hematopoietic transformation.
Alternate Accession IDs
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation and reactive oxygen species scavenging in skeletal muscle and other tissues, and these processes are thought to be critical to the benefits of CR. PGC-1a is a transcriptional coactivator that regulates mitochondrial function and is induced by CR. Consequently, many of the mitochondrial and metabolic benefits of CR are attributed to increased PGC-1a activity. To test this model for the first time, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle PGC-1a (MKO). Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1a is dispensable for the whole-body benefits of CR. In contrast, gene expression profiling and electron microscopy demonstrated that PGC-1a is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1a is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1a nor mitochondrial biogenesis in skeletal muscle are required for the metabolic benefits of CR.
Publication Title
Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
mTOR and HDAC inhibitors induce cell death of malignant peripheral nerve sheath tumors (MPNSTs) in vitro, and in vivo
Publication Title
mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors.
Alternate Accession IDs
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumor cells exhibit aberrant metabolism characterized by high glycolysis even in the presence of oxygen. This metabolic reprogramming, known as the Warburg effect, provides tumor cells with the substrates and redox potential required for the generation of biomass. Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect. SIRT3 loss promotes a metabolic profile consistent with high glycolysis required for anabolic processes in vivo and in vitro. Mechanistically, SIRT3 mediates metabolic reprogramming independently of mitochondrial oxidative metabolism and through HIF1a, a transcription factor that controls expression of key glycolytic enzymes. SIRT3 loss increases reactive oxygen species production, resulting in enhanced HIF1a stabilization. Strikingly, SIRT3 is deleted in 40% of human breast cancers, and its loss correlates with the upregulation of HIF1a target genes. Finally, we find that SIRT3 overexpression directly represses the Warburg effect in breast cancer cells. In sum, we identify SIRT3 as a regulator of HIF1a and a suppressor of the Warburg effect.
Publication Title
SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BACKGROUND & AIMS: Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition driven by loss of homeostasis between the mucosal immune system, the commensal gut microbiota, and the intestinal epithelium. Our overarching goal is to understand how these components of the intestinal ecosystem cooperate to control homeostasis and to identify novel signal transduction pathways that become dysregulated in IBD. METHODS: We have applied a multi-scale systems biology approach to a mouse model of chronic colitis. We combined quantitative measures of epithelial hyperplasia and immune infiltration with multivariate analysis of inter- and intra-cellular signaling molecules in order to generate a tissue level model of the inflamed disease state. We utilized the computational model to identify signaling pathways that were dysregulated in the context of colitis and then validated model predictions by measuring the effect of small molecule pathway inhibitors on colitis. RESULTS: Our data-driven computational model identified mTOR signaling as a potential driver of inflammation and mTOR inhibition reversed the molecular, immunological, and epithelial manifestations of colitis. Inhibition of Notch signaling, which induces epithelial differentiation, had the same effect, suggesting that the epithelial proliferation/differentiation state plays a key role in maintaining homeostasis of the colon. Confirming this, we found that colonic organoids grown ex vivo showed a similar relationship between proliferation and cytokine expression, even in the absence of gut bacteria and immune cells. CONCLUSIONS: Our study provides a tissue-level systems biology perspective of murine colitis and suggests that mTOR plays a key role in regulating colonic homeostasis by controlling epithelial proliferation/differentiation state.
Publication Title
The colonic epithelium plays an active role in promoting colitis by shaping the tissue cytokine profile.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 671 Downloadable Samples
- Illumina HiSeq 2500
Description
To define molecular markers of tyrosine kinase inhibitor-induced cardiotoxicity, we measured transcriptome changes in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) treated with one of four tyrosine kinase inhibitors (Erlotinib, Lapatinib, Sorafenib, or Sunitinib) displaying a range of mild to severe cardiotoxicity or a vehicle-only control (DMSO). Gene expression changes were assessed at the cell population level using total RNA-seq, which measured levels of both mRNAs and non-coding RNAs. hiPSC-CMs used in this study were the Cor.4U cells purchased from Ncardia. Overall design: hiPSC-CMs were treated with each TKI (Erlotinib, Lapatinib, Sorafenib or Sunitinib) at three doses (1, 3 and 10 µM) for 24 hours and the intermediate dose (3 µM) for an additional three time points (6h, 72h and 168h). hiPSC-CMs were also treated with the DMSO vehicle-only control at four time points (6h, 24h, 72h and 168h). Each treatment condition had three biological replicates, collected from three independent experiments using three different lots of hiPSC-CMs. Total RNA was collected from all these samples.
Publication Title
Adaptation of Human iPSC-Derived Cardiomyocytes to Tyrosine Kinase Inhibitors Reduces Acute Cardiotoxicity via Metabolic Reprogramming.
Alternate Accession IDs
Sample Metadata Fields
Sex, Specimen part, Subject, Compound, Time
View Samples- Mus musculus
- 5 Downloadable Samples
- NextSeq 500
Description
Sirtuin 3 (SIRT3) is an NAD+-dependent deacetylase downregulated in aging and age-associated diseases such as cancer and neurodegeneration, and high fat diet (HFD)-induced metabolic disorders. Thus, we performed a small molecule screen and identified an unexpected metabolic vulnerability associated with SIRT3 loss. Overall design: RNA sequencing in SV40T immortalized SIRT3 WT (triplicates) and SIRT3 KO MEF (duplicates) lines under normal conditions.
Publication Title
Small-Molecule Screen Identifies De Novo Nucleotide Synthesis as a Vulnerability of Cells Lacking SIRT3.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Subject
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