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SRP184537
Mus musculus
12 Downloadable Samples
NextSeq 500
Description
Because injured mitochondria can accelerate cell death through the elaboration of oxidative free radicals and other mediators, it is somewhat paradoxical that proliferator gamma coactivator 1-alpha (PGC1a), a stimulator of increased mitochondrial abundance, protects stressed renal cells instead of potentiating injury. Here we report that PGC1a's induction of lysosomes via transcription factor EB (TFEB) may be pivotal for kidney protection. CRISPR and stable gene transfer showed that PGC1a knockout tubular cells were sensitized to the genotoxic stressor cisplatin whereas transgenic cells were protected. The biosensor mtKeima unexpectedly revealed that cisplatin blunts mitophagy both in cells and mice. PGC1a not only counteracted this effect but also raised basal mitophagy, as did the downstream mediator nicotinamide adenine dinucleotide (NAD+). PGC1a did not consistent affect known autophagy pathways modulated by cisplatin. Instead RNA sequencing identified coordinated regulation of lysosomal biogenesis via TFEB. This effector pathway was sufficiently important that inhibition of TFEB or lysosomes unveiled a striking harmful effect of excess PGC1a in cells and conditional mice. These results uncover an unexpected effect of cisplatin on mitophagy and PGC1a's exquisite reliance on lysosomes for kidney protection. Finally, the data illuminate TFEB as a novel target for renal tubular stress resistance. Overall design: 12 samples in total = 3 replicates each from 4 groups
Publication Title
TFEB-driven lysosomal biogenesis is pivotal for PGC1α-dependent renal stress resistance.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 207 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bone marrow macrophages were cultured from 16 week old apoE-deficient F2 mice from an AKRxDBA/2 intercross
Publication Title
Sex specific gene regulation and expression QTLs in mouse macrophages from a strain intercross.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
While early stages of clear cell renal cell carcinoma (ccRCC) are curable, survival outcome for metastatic ccRCC remains poor. The purpose of the current study was to apply a new individualized bioinformatics analysis (IBA) strategy to these transcriptome data in conjunction with Gene Set Enrichment Analysis of the Connectivity Map (C-MAP) database to identify and reposition FDA-approved drugs for anti-cancer therapy. We demonstrated that one of the drugs predicted to revert the RCC gene signature towards normal kidney, pentamidine, is effective against RCC cells in culture and in a RCC xenograft model. Most importantly, pentamidine slows tumor growth in the 786-O human ccRCC xenograft mouse model. To determine which genes are regulated by pentamidine in a human RCC cell line, 786-O, we treated these cells with pentamidine and performed transcriptional profiling analysis.
Publication Title
Computational repositioning and preclinical validation of pentamidine for renal cell cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 69 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mind-body practices that elicit the relaxation response (RR) have been used worldwide for millennia to prevent and treat disease. The RR is believed to be the counterpart to stress response and is characterized by decreased oxygen consumption, increased exhaled nitric oxide, and reduced psychological distress. Individuals experiencing chronic psychological stress have the opposite pattern of physiology and a characteristic transcriptional profile. We hypothesized that consistent, long-term practice of RR techniques results in characteristic changes in gene expression. We tested this hypothesis by assessing the transcriptional profile of whole blood in healthy, long-term practitioners of daily RR practice (group M) in comparison to healthy controls (group N1). The signature obtained has been validated on new subject data.
Publication Title
Genomic counter-stress changes induced by the relaxation response.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We profiled genome-wide gene expression of human prostate benign and malignant tissue to identify potential biomarkers and immunotherapy targets.
Publication Title
Identification of the transcription factor single-minded homologue 2 as a potential biomarker and immunotherapy target in prostate cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study was performed to understand the gene expression changes that accompany treatment of renal cell carcinoma (RCC) with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy. Human RCC cell lines were implanted into the flanks of nude beige mice, allowed to reach 12mm in long axis, and then treated with TKIs (sunitinib or sorafenib). Tumors were excised at 2 timepoints (prior to any therapy and at the 20mm endpoint of the study) and gene expression analysis was performed.
Publication Title
Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
Gene expression profiling on stomach and colon tissue from Spdef knockout, heterozygous and wild type mice.
Publication Title
Requirement of the epithelium-specific Ets transcription factor Spdef for mucous gland cell function in the gastric antrum.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Iron overload causes the generation of reactive oxygen species, which can lead to lasting damage to the liver and other organs. We studied the effects of iron deficiency and iron overload on the hepatic transcriptional and metabolomic profile in mouse models. Overall design: We studied effect of different iron overloads (High, medium and Low) on liver transcriptome using whole genome transcriptome profiling.
Publication Title
Nicotinamide N-methyltransferase expression decreases in iron overload, exacerbating toxicity in mouse hepatocytes.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
ERG (Ets Related Gene) is an ETS transcription factor that was originally described for its role in a number of human cancers. Our preliminary data demonstrate that ERG exhibits a highly EC restricted pattern of expression in cultured primary cells and several adult tissues including the heart, lung, and brain. In response to inflammatory stimuli, such as TNF-alpha, we observed a marked reduction of ERG expression in EC.
Publication Title
Antiinflammatory effects of the ETS factor ERG in endothelial cells are mediated through transcriptional repression of the interleukin-8 gene.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Iron overload causes the generation of reactive oxygen species, which can lead to lasting damage to the liver and other organs. We studied the effects of iron deficiency and iron overload on the hepatic transcriptional and metabolomic profile in mouse models. Overall design: We studied effect of different iron deficiency by HJV gene knockout mice on liver transcriptome using whole genome transcriptome profiling.
Publication Title
Nicotinamide N-methyltransferase expression decreases in iron overload, exacerbating toxicity in mouse hepatocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples