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GSE31208
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Frataxin deficiency in human is the cause of Friedreich's ataxia (FA), a lethal neuro- and cardio-degenerative disease. Knock-out (KO) mice of this mouse model of FA exhibit classical cardiomyopathy of the patients. The onset of FA phenotypes in the KO mice is approximately 6-7 weeks of age. This genearray analysis was conducted to examine the changes in gene expression in the heart of KO mice relative to their wild-type (WT) littermates at 4- and 10-weeks of age. At 10-weeks of age, the KO mice begin to die from severe cardiomyopathy.
Publication Title
Elucidation of the mechanism of mitochondrial iron loading in Friedreich's ataxia by analysis of a mouse mutant.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: The goal of this study was to map the pathway of mRNA decay by human RNase L Methods: Total RNA was extracted (RNeasy kit, Qiagen). RNA integrity was verified by an RNA 6000 Nano Chip, using BioAnalyzer and 2100 Expert software (Agilent Technologies). The mRNA was enriched by oligo-dT pulldown from total RNA, followed by fragmentation, adapter ligation, PCR amplification, and finally sequencing on Illumina HiSeq 2000 platform. For sequencing introns, the oligo-dT pulldown step was replaced with Ribo-Zero rRNA removal (Illumina). Sequencing reads were mapped to the human genome hg19 using TopHat 2 set to map stranded reads with default parameters. Mapped read counts were obtained using HTseq-count run in union mode. Results: We developed an approach for transcriptome-wide profiling of RNase L activity in human cells and identified hundreds of direct RNA targets and non-targets. We show that this RNase L-dependent decay (RLDD) selectively affects transcripts regulated by miR-17/miR-29/miR-200 and other microRNAs that function as suppressors of mammalian cell adhesion and proliferation. RNase L mimics the effects of these microRNAs and acts as a suppressor of proliferation and adhesion in mammalian cells. Conclusions: Our data suggest that RLDD serves to establish an anti-proliferative state via destabilization of the microRNA-regulated transcriptome. Overall design: Human mRNA profiles from HeLa, T47D and HAP1 cells were generated by deep sequencing using Illumina Illumina HiSeq 2000.
Publication Title
Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We demonstrated recently that both constitutive and FAS-triggered apoptosis of human neutrophils are profoundly impaired by Francisella tularensis, but how this is achieved is largely unknown. To test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, we used human oligonucleotide microarrays to identify differentially regulated genes in cells infected with F. tularensis strain LVS compared with uninfected controls.
Publication Title
Francisella tularensis alters human neutrophil gene expression: insights into the molecular basis of delayed neutrophil apoptosis.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are often caused by strains encoding Panton-Valentine leukocidin (PVL). PVL can cause lysis of polymorphonuclear leukocytes (PMNs) and other myeloid cells in vitro, a function considered widely as the primary means by which PVL might contribute to disease. However, at sublytic concentrations PVL can function as a PMN agonist. To better understand this phenomenon, we investigated the ability of PVL to alter human PMN function. PMNs exposed to PVL had enhanced capacity to produce superoxide in response to N-formyl-methionyl-leucyl-phenylalanine (fMLF), but unlike priming by lipopolysaccharide, this response did not require Toll-like receptor signal transduction. On the other hand, there was subcellular redistribution of NADPH oxidase components in PMNs following exposure of these cells to PVL - a finding consistent with priming. Priming of PMNs with other agonists such as IL-8 or GM-CSF altered the ability PVL to cause formation of pores in the plasma membranes of these cells. Microarray analysis revealed significant changes in the human PMN transcriptome following exposure to PVL, including up-regulation of molecules that regulate the inflammatory response. Consistent with the microarray data, mediators of the inflammatory response were released from PMNs after stimulation with PVL. We conclude that exposure of human PMNs to sublytic concentrations of PVL elicits a proinflammatory response that is regulated in part at the level of gene expression. We propose that PVL-mediated priming of PMNs enhances the host innate immune response.
Publication Title
Sublytic concentrations of Staphylococcus aureus Panton-Valentine leukocidin alter human PMN gene expression and enhance bactericidal capacity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is becoming increasingly apparent that Staphylococcus aureus are able to survive engulfment by macrophages, and that the intracellular environment of these cells, which is essential to innate host defenses against invading microorganisms, may in fact provide a refuge for staphylococcal survival and dissemination. Based on this, we postulated that S. aureus might induce cytoprotective mechanisms by changing gene expression profiles inside macrophages similar to obligate intracellular pathogens, such as Mycobacterium tuberculosis.
Publication Title
Phagocytosis of Staphylococcus aureus by macrophages exerts cytoprotective effects manifested by the upregulation of antiapoptotic factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In the present study, we hypothesized that C/EBPa (CCAAT/enhancer-binding protein alpha) plays a role in cell regeneration in response to bronchiolar epithelial cell injury. C/EBPa mediated ciliated cell regeneration after naphthalene bronchiolar epithelial cell injury in vivo. Furthermore, we demonstrated that C/EBPa regulates protease/anti-protease balance after lung injury, and intratracheal treatment with anti-protease (BPTI) restored ciliated cell regeneration after naphthalene injury in CebpaD/D mice.
Publication Title
CCAAT/enhancer binding protein-α regulates the protease/antiprotease balance required for bronchiolar epithelium regeneration.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
The maturation of dendritic cells (DCs) after exposure to microbial products or inflammatory mediators plays a critical role in initiating the immune response. We found that maturation can also occur under steady state conditions, triggered by alterations in E-cadherin-mediated DC-DC adhesion. Selective disruption of these interactions induced the typical features of DC maturation including the upregulation of costimulatory molecules, MHC class II, and chemokine receptors. These events were triggered at least in part by activation of the b-catenin pathway. However, unlike maturation induced by microbial products, E-cadherin-stimulated DCs failed to release immunostimulatory cytokines, exhibiting an entirely different transcriptional profile. As a result, E-cadherin-stimulated DCs elicited an entirely different T cell response in vivo, generating T cells with a regulatory as opposed to an effector phenotype. These DCs induced tolerance in vivo and may thus contribute to the elusive steady state tolerogenic DCs.
Publication Title
Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Deletion of Stat3 induced genes influencing protein metabolism, transport, chemotaxis and apoptosis and decreased the expression of genes mediating lipid synthesis and metabolism. Srebf1 and 2, key regulators of fatty acid and steroid biosynthesis, were decreased in Stat3D/D mice. Stat3 influenced both pro- and anti-apoptotic pathways, regulating and maintaining the balance between a subset of pro- and anti-apoptotic genes that determine cell death or survival. Akt, a known target of Stat3, participates in many Stat3 mediated pathways including Jak-Stat signaling, apoptosis, the MAPK signaling, cholesterol and fatty acid biosynthesis. Deletion of Stat3 from type II epithelial cells altered the expression of genes regulating diverse cellular processes, including cell growth and apoptosis, lipid biosynthesis and metabolism. Stat3 regulates cell formation through a complex regulatory network that likely enhances alveolar epithelial cell survival and surfactant/lipid synthesis, necessary for the protection of the lung during injury.
Publication Title
Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We have previously demonstrated that deletion of the Cebpa gene in the developing fetal mouse lung caused death soon after birth from the failure of lung maturation. Many of the transcriptional pathways regulating morphogenesis of the fetal lung are induced postnatally and mediate repair of the injured lung. We hypothesized that C/EBPa plays a role in protection of the alveolar epithelium following hyperoxia injury of the mature lung. Transgenic Cebpa/ mice in which Cebpa was conditionally deleted from Clara cells (from early gestation) and type II cells (from near-term) were developed. Cebpa/ mice grow normally without any pulmonary abnormalities. Cebpa/ mice were highly susceptible to hyperoxia. Cebpa/ mice died within 4d after hyperoxia associated with severe lung inflammation and altered surfactant components at a time when all control mice survived. Microarrays were analyzed on isolated type II cells at an early stage (24h) of hyperoxia exposure to detect the primary genes influenced by deletion of Cebpa. The associated network analysis revealed the reduced expression of key genes related to surfactant lipid and protein homeostasis, such as Srebf, Scap, Lpcat1, Abca3, Sftpb, and Napsa. Genes for the cell signaling, immune response, and protective antioxidants, including GSH and Vnn-1,3, were decreased in the Cebpa/ mice lung. C/EBPa did not play a critical role in postnatal pulmonary function under normal conditions. In contrast, in the absence of C/EBPa, exposure to hyperoxia caused respiratory failure, supporting the concept that C/EBPa plays an important role in enhancing epithelial cell survival, surfactant lipid homeostasis, and maturation of SP-B from pro-SP-B.
Publication Title
C/EBP{alpha} is required for pulmonary cytoprotection during hyperoxia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung.
Sample Metadata Fields
Specimen part
View Samples