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GSE57048
Mus musculus
11 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death globally, is influenced by both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as a candidate COPD susceptibility gene based on genetic association studies, with IRP2 increased in the lungs of COPD patients. Here we demonstrate that mice deficient in IRP2 are protected from cigarette smoke (CS)-induced COPD. Using RIP-Seq, RNA-Seq, gene expression and pathway analysis, we identify IRP2 as a regulator of mitochondrial function in the lung. We show that an increase in IRP2 results in a cytochrome c oxidase (COX)-dependent alteration in oxidative capacity and mitochondrial-iron dysfunction involving frataxin. We demonstrate that mice with impaired COX or frataxin activity have altered responses to CS and show that overexpressing IRP2 in vivo alters mitochondrial dynamics. These data suggest a critical role of the mitochondria-iron axis in mediating the pathogenesis of COPD.
Publication Title
Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- 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- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The Clade A PP2C Highly ABA-Induced1 (HAI1, At5g59220) is strongly up-regulated by low water potential in an ABA-dependent manner. Using knockout mutants of hai1, we found that HAI1 functions as a negative regulator of low water potential-induced proline and osmoregulatory solute accumulation. We also found a relatively weak and limited interaction of HAI1 with the RCAR/PYL family of ABA receptors. This, plus its induced expression, suggest that HAI1 remains active during stress and attenuates specific aspects of drought response.
Publication Title
Unique drought resistance functions of the highly ABA-induced clade A protein phosphatase 2Cs.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Two Clade E Growth Regulating PP2Cs EGR1 and EGR2 (EGR1, At3g05640; EGR2, At5g27930) are strongly up regulated by low water but much less affected by ABA. EGR mutants maintained higher seedling root elongation and dry weight at low water potential and higher levels of stress protective metabolite proline.
Publication Title
Protein Phosphatase 2Cs and <i>Microtubule-Associated Stress Protein 1</i> Control Microtubule Stability, Plant Growth, and Drought Response.
Sample Metadata Fields
Age, 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
- 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- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Histone deacetylase 3 (HDAC3) is the catalytic component of NCoR/SMRT corepressor complexes that mediate the actions of transcription factors implicated in the regulation of B cell development and function. We crossed Hdac3 conditional knockout mice with Mb1-Cre knockin animals to delete Hdac3 in early progenitor B cells. The spleens of Hdac3F/-Mb1-Cre+/- mice were virtually devoid of mature B cells, and B220+CD43+ B cell progenitors accumulated within the bone marrow. Quantitative deep sequencing of the immunoglobulin heavy chain locus from B220+CD43+ populations identified a defect in VHDJH recombination with a severe reduction in productive rearrangements, which directly corresponded to the loss of pre-B cells from Hdac3D/- bone marrow. For Hdac3D/- B cells that did show productive VDJ rearrangement, there was significant skewing toward the incorporation of proximal VH gene segments and a corresponding reduction in distal VH gene segment usage. While transcriptional effects within these loci were modest, Hdac3D/- progenitor cells displayed global changes in chromatin structure that likely hindered effective distal V-DJ recombination. Re-introduction of wild type Hdac3 restored normal B cell development, whereas an Hdac3 point mutant lacking deacetylase activity failed to complement this defect. Thus, the deacetylase activity of Hdac3 is required for the generation of mature B cells. Overall design: Bone marrow was isolated from Hdac3+/+Mb1cre+/- or Hdac3F/-Mb1cre+/- mice at 8 weeks of age. B220+CD43+ B cells were isolated from marrow by FACS and cells from two mice were pooled per sample. Total RNA isolated by Trizol extraction.
Publication Title
Deacetylase activity of histone deacetylase 3 is required for productive <i>VDJ</i> recombination and B-cell development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 1 Downloadable Sample
- NextSeq 500
Description
Gjd3-CreEGFP mice is a novel genetic tool to study the structural and molecular signatures of Atrioventricular Node (AVN) at a high resolution. Overall design: Focusing on the cardiac conduction system, we developed and rigorously characterized a geentic tool Gjd3-CreEGFP to perform in-depth analysis of AVN structure and composition. Utilizing this AVN-specific mouse model, we performed scRNA-Seq on neonatal Gjd3-CreEGFP mice to guide our single-cell atlas of the Atrio-ventricular conduction system (AVCS).
Publication Title
Using Gjd3-CreEGFP mice to examine atrioventricular node morphology and composition.
Sample Metadata Fields
Specimen part, Subject
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