Filters
Technology
Platform
GSE13035
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
Cellular stress responses can be activated following functional defects in organelles such as mitochondria and the endoplasmic reticulum. Mitochondrial dysfunction caused by loss of the serine protease HtrA2 leads to a progressive movement disorder in mice and has been linked to parkinsonian neurodegeneration in humans. Here we demonstrate that loss of HtrA2 results in transcriptional up-regulation of nuclear genes characteristic of the integrated stress response, including the transcription factor CHOP, selectively in the brain. We also show that loss of HtrA2 results in the accumulation of unfolded proteins in the mitochondria, defective mitochondrial respiration and enhanced production of reactive oxygen species that contribute to the induction of CHOP expression and to neuronal cell death. CHOP expression is also significantly increased in Parkinsons disease patients brain tissue. We therefore propose that this brain-specific transcriptional response to stress may be important in the advance of neurodegenerative diseases.
Publication Title
Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Cellular stress responses can be activated following functional defects in organelles such as mitochondria and the endoplasmic reticulum. Mitochondrial dysfunction caused by loss of the serine protease HtrA2 leads to a progressive movement disorder in mice and has been linked to parkinsonian neurodegeneration in humans. Here we demonstrate that loss of HtrA2 results in transcriptional up-regulation of nuclear genes characteristic of the integrated stress response, including the transcription factor CHOP, selectively in the brain. We also show that loss of HtrA2 results in the accumulation of unfolded proteins in the mitochondria, defective mitochondrial respiration and enhanced production of reactive oxygen species that contribute to the induction of CHOP expression and to neuronal cell death. CHOP expression is also significantly increased in Parkinsons disease patients brain tissue. We therefore propose that this brain-specific transcriptional response to stress may be important in the advance of neurodegenerative diseases.
Publication Title
Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Cellular stress responses can be activated following functional defects in organelles such as mitochondria and the endoplasmic reticulum. Mitochondrial dysfunction caused by loss of the serine protease HtrA2 leads to a progressive movement disorder in mice and has been linked to parkinsonian neurodegeneration in humans. Here we demonstrate that loss of HtrA2 results in transcriptional up-regulation of nuclear genes characteristic of the integrated stress response, including the transcription factor CHOP, selectively in the brain. We also show that loss of HtrA2 results in the accumulation of unfolded proteins in the mitochondria, defective mitochondrial respiration and enhanced production of reactive oxygen species that contribute to the induction of CHOP expression and to neuronal cell death. CHOP expression is also significantly increased in Parkinsons disease patients brain tissue. We therefore propose that this brain-specific transcriptional response to stress may be important in the advance of neurodegenerative diseases.
Publication Title
Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Primary diffuse large B cell lymphomas of different immune-privileged sites (IP-DLBCL) share many clinical and biological features, such as a relatively poor prognosis, preferential dissemination to other immune-privileged sites and deletion of the HLA region, which suggests that IP-DLBCL represents a separate entity. To further investigate the nature of IP-DLBCL, we investigated site-specific genomic aberrations in 16 testicular, 9 central nervous system (CNS) and 15 nodal DLBCL using array-CGH. We also determined minimal common regions of gain and loss. Using robust algorithms, the array-CGH data were combined with gene expression data to explore pathways deregulated by chromosomal aberrations.
Publication Title
Genomic alterations and gene expression in primary diffuse large B-cell lymphomas of immune-privileged sites: the importance of apoptosis and immunomodulatory pathways.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 103 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Preterm infants are susceptible to neonatal inflammatory/infective diseases requiring drug therapy. The present study hypothesized that mRNA expression in the blood may be modulated by signaling pathways during treatment. The current study aimed to explore changes in global gene expression in the blood from preterm infants with the objective of identifying patterns or pathways of potential relevance to drug therapy. The infants involved were selected based on maternal criteria indicating increased risk for therapeutic intervention. Global mRNA expression was measured in 107 longitudinal whole blood samples using Affymetrix Human Genome U133 Plus 2.0 arrays; samples were obtained from 20 preterm infants. Unsupervised clustering revealed a distinct homogeneous gene expression pattern in 13 samples derived from seven infants undergoing continuous oxygen therapy. At these sampling times, all but one of the seven infants exhibited severe drops in peripheral capillary saturation levels below 60%. The infants were reoxygenated with 100% inspired oxygen concentration. The other samples (n=94) represented the infants from the cohort at time points when they did not undergo continuous oxygen therapy. Comparing these two sets of samples identified a distinct gene expression pattern of 5,986 significantly differentially expressed genes, of which 5,167 genes exhibited reduced expression levels during transient hypoxia. This expression pattern was reversed when the infants became stable, i.e., when they were not continuously oxygenated and had no events of hypoxia. To identify signaling pathways involved in gene regulation, the Database for Annotation, Visualization and Integrated Discovery online tool was used. Mitogen activated protein kinases, which are normally induced by oxidative stress, exhibited reduced gene expression during hypoxia. In addition, nuclear factor erythroid 2 related factor 2 antioxidant response element target genes involved in oxidative stress protection were also expressed at lower levels, suggesting reduced transcription of this pathway. The findings of the present study suggest that oxidative stress dependent signaling is reduced during hypoxia. Understanding the molecular response in preterm infants during continuous oxygenation may aid in refining therapeutic strategies for oxygen therapy.
Publication Title
Gene expression profiles in preterm infants on continuous long‑term oxygen therapy suggest reduced oxidative stress‑dependent signaling during hypoxia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We established chromate transformed cell lines by chronic exposure of normal human bronchial epithelial BEAS-2B cells to low doses of hexavalent chromium followed by anchorage-independent growth. The gene expression profiles were analyzed in the established cell lines.
Publication Title
Comparison of gene expression profiles in chromate transformed BEAS-2B cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Piwi proteins and Piwi-interacting small RNAs (piRNAs) have known functions in transposon silencing in the male germline of fetal and newborn mice. Both are also necessary for spermatogenesis in adult testes, however, their function here remains a mystery. Here, we use germ cell isolations and small RNA sequencing to show that most piRNAs in meiotic spermatocytes originate from clusters in intergenic non-repeat regions of DNA. The regulation of these piRNA clusters, including the processing of the precursor transcripts into individual piRNAs, is accomplished through mostly unknown processes. We present evidence for a regulatory mechanism for one such cluster, named cluster 1082B, located on chromosome 7 in the mouse genome, containing 788 unique piRNAs. The precursor transcript and individual piRNAs within the cluster are repressed by the Alkbh1 dioxygenase and the transcription repressor Tzfp, which are believed to be interaction partners in testis. We observe more than a thousand-fold upregulation of individual piRNAs in pachytene spermatocytes isolated from Alkbh1-/- and TzfpGTi/GTi testes. Repression is further supported by the identification of a 10 bp Tzfp recognition sequence contained within the precursor transcript. Downregulation of long interspersed elements 1 (LINE1) and intracisternal A-particle (IAP) transcripts in the Alkbh1-/- and TzfpGTi/GTi testes leads us to propose a potential role for the 1082B-encoded piRNAs in transposon silencing. Overall design: Characterization of small RNAs in mouse pachytene spermatocytes for wild-type (WT) and Alkbh1-/- and TzfpGTi/GTi, and mRNA in mouse pachytene spermatocytes for wild-type (WT) and Alkbh1-/-
Publication Title
Alkbh1 and Tzfp repress a non-repeat piRNA cluster in pachytene spermatocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung, and bladder cancers, and cardiovascular disease. The mechanisms behind arsenic's effects remain unclear, but recent research indicates that aresnic acts along sex-specific lines and may be an endocrine disruptor. The objective of this study was to evaluate the nature of gene expression chagnes among males and females exposed to arsenic contaminated water in Bangladesh at high and low dose exposures.The median wAs concentration for the low exposure group was 103 g/L for males and 117 g/L for females (range 50200 g/L). For the high exposure group, the median wAs concentration was 355 g /L for males (range 250-500 g /L) and 434 g/L for females (range 2321000 g /L). The PBMCs of males with high exposure compared to those with low exposure there were 534 differentially expressed genes (p <0.05); and for females with high exposure relative to low exposure there were 645 differentially expressed genes (p <0.05) in PBMCs of females.
Publication Title
Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Sequentially acting Sox transcription factors in neural lineage development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
We report sequential binding but unique functions of different Sox transcription factors during distinct stages of neural differentiation
Publication Title
Sequentially acting Sox transcription factors in neural lineage development.
Sample Metadata Fields
Specimen part
View Samples