Filters
Technology
Platform
GSE117028
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disorder caused by a polyglutamine-encoding CAG repeat expansion in the ATXN3 gene, which encodes a deubiquitinating enzyme, ATXN3, implicated in numerous quality control pathways. Several mechanisms have been proposed to explain the pathogenic role of mutant polyQ-expanded ATXN3 in SCA3 including disease protein aggregation, impairment of ubiquitin-proteasomal degradation and transcriptional dysregulation. A better understanding of the normal functions of this protein may shed light on SCA3 disease pathogenesis. To assess the potential normal role of ATXN3 in regulating transcription, we compared gene expression profiles in wildtype (WT) versus Atxn3 knockout (KO) mouse embryonic fibroblasts (MEFs).
Publication Title
Loss of the Spinocerebellar Ataxia type 3 disease protein ATXN3 alters transcription of multiple signal transduction pathways.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Deficiencies in the ATM gene are the underlying cause for ataxia telangiectasia, a congenital syndrome characterized by neurological, motor and immunological defects, as well as a predisposition to cancer risks. MicroRNAs (miRNAs) are small regulators of post-transcriptional gene expression and a useful tool for cancer diagnosis, staging, and prediction of therapeutic responses to clinical regimens. In particular, miRNAs have been used to develop signatures for breast cancer profiling. We are interested in the consequences of ATM deficiency on miRNA expression in breast epithelial cells and the potential contribution to cancer predisposition. In this study we investigate the effects of ATM loss on the miRNA expression and related gene expression changes in normal human mammary epithelial cells (HME-CC). We have identified 81 significantly differently expressed miRNAs in the ATM-deficient HME-CCs using small RNA sequencing. Many of these differentially expressed miRNAs have been described and implicated in tumorigenesis and proliferation. These changes include down-regulation of tumor suppressor miRNAs, such as hsa-miR-29c and hsa-miR-16, as well as the over-expression of pro-oncogenic miRNAs hsa-miR-93 and hsa-mir-221. All 81 miRNAs were combined with genome wide gene expression profiles to investigate possible targets of miRNA regulation. We identified messenger RNA (mRNA) targets of these miRNAs that were also significantly regulated after the depletion of ATM. Predicted targets included many genes implicated in cancer formation and progression, including SOCS1 and the proto-oncogene MAF. Integrated analysis of miRNA and mRNA expression allows us to build a more complete understanding of the pathways and networks involved in the breast cancer predisposition observed in individuals deficient in ATM. This study highlights miRNA and predicted mRNA target expression changes in ATM-deficient HME-CCs and suggests a mechanism for the breast cancer-prone phenotype seen in ATM deficient cells and patients. Additionally, this study provides preliminary data for defining miRNA profiles that may be used prognostic biomarkers for breast cancer predisposition. Overall design: Examination of small RNA population in human mammary epithelial cell lines. Each condition was preformed in triplicate.
Publication Title
Genome-wide small RNA sequencing and gene expression analysis reveals a microRNA profile of cancer susceptibility in ATM-deficient human mammary epithelial cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 506 Downloadable Samples
- Illumina HiSeq 2000
Description
The study examined early transcriptional changes in the brain of different mouse models of spinocerebellar ataxia type 3, a dominantly-inherited neurodegenerative disease caused by a CAG repeat expansion in the ATXN3 gene. The goal was to identify early transcriptional signatures that are strongly associated with the accumulation and aggregation of the disease protein, ataxin-3, in the brain. The study also investigated the extent to which the observed transcriptional changes might be contributors to disease pathogenesis. Overall design: The overall study includes multiple different RNA-seq runs utilizing wild-type, two different knock-in mouse models of SCA3 (a traditional and variant), two different transgenic models of SCA3 (Q84 and Q15), and an ataxin-3 knock-out mouse. In total, 19 wild-type mice, 13 homozygous variant knock-in mice, 6 heterozygous variant knock-in mice, 4 traditional homozygous knock-in mice, 4 traditional heterozygous knock-in mice, 4 Q84 transgenic mice, 4 Q15 transgenic mice, and 3 ataxin-3 knock-out mice. The majority of the study examined the pons of the mice, and with one smaller run examining the deep cerebellar nuclei of wild-type and variant homozygous knock-in mice (n=3 each).
Publication Title
Comparison of spinocerebellar ataxia type 3 mouse models identifies early gain-of-function, cell-autonomous transcriptional changes in oligodendrocytes.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The objective of this set of samples is to identify genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by ionizing radiation in wild-type murine pre-B cells. The data generated in this project will be compared to the data generated in GSE9024, in which genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by the Rag proteins in murine pre-B cells were examined. In order to understand the differences between the physiologic and genotoxic responses to DSB DNA damage, we need to compare cells that are all in the same compartment of the cell cycle. We are therefore examining the response to IR-induced damage in cells that are arrested in G1, which would correspond to our previous study of G1 arrested cells with Rag-induced breaks. This will illuminate the difference directly, allowing us to better understand the signaling responses to the different types of DNA damage.
Publication Title
DNA damage activates a complex transcriptional response in murine lymphocytes that includes both physiological and cancer-predisposition programs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The objective is to identify genes that are differentially expressed following the introduction of DNA double-strand breaks (DSBs) by the Rag proteins in murine pre-B cells. Cells lacking Artemis are used since the Rag-induced DSBs will not be repaired, and thus, will provide a continuous stimulus to the cell.
Publication Title
DNA damage activates a complex transcriptional response in murine lymphocytes that includes both physiological and cancer-predisposition programs.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Physiologically relevant concentrations of retinoic acid are added to Mouse ES cells and a time course (0-72 hours) is examined with expression tiling arrays and RNA-seq to characterize the early dynamics of expression of coding and non-coding RNAs in and around the Hox clusters. Overall design: Gene expression is examined at various timepoints (0-72 hrs) after retinoic acid induced neuronal differentiation
Publication Title
Dynamic regulation of Nanog and stem cell-signaling pathways by Hoxa1 during early neuro-ectodermal differentiation of ES cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 120 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The use of calcineurin inhibitor (CI) immunosuppressants has significantly improved the early allograft survival rate in organ transplantation. However, CI therapy has been associated with chronic nephrotoxicity, which limits their long-term utility. In order to understand the mechanisms of the toxicity, we analyzed the gene expression changes that underlie the development of CI immunosuppressant-mediated nephrotoxicity, in male Sprague-Dawley (SD) rats dosed daily with cyclosporine (CsA), FK506 or rapamycin (Rapa) for 1 to 28 days. We identified a group of genes, whose expression in rat kidney is quantitatively correlated with CI-induced kidney injury as observed in changes in blood urea nitrogen (BUN) levels and kidney histopathology. These genes include both up-regulated genes, such as Ren1 and Klks3, and down-regulated genes, such as Calb1, Egf, NCC, and kidney specific Wnk1 (KS-Wnk1). Using the down-regulated genes alone we successfully predicted CI immunosuppressant-mediated kidney injury in rats following 7 days of treatment. Among these genes are two mechanism-related genes, NCC and KS-Wnk1, both of which are involved in the sodium transport in the distal nephrons. The down-regulation of both genes at the mRNA and protein level in rat kidney following CI treatment was confirmed by quantitative RT-PCR and immunohistochemical staining, respectively. We hypothesize that decreased expression of NCC may cause reduced sodium chloride reabsorption in the distal tubules, and contribute to the prolonged activation of the Renin-Angiotensin-System (RAS), a demonstrated contributor to the development of CI-induced nephrotoxicity in both animal models and clinical settings. Therefore, NCC and KS-Wnk1 could potentially be used as biomarkers for early detection and prevention of CI-related nephrotoxicity in clinical practice.
Publication Title
Genomic-derived markers for early detection of calcineurin inhibitor immunosuppressant-mediated nephrotoxicity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This file contains gene microarray data from FACS purified mouse high endothelial cells and capillary endothelial cells from peripheral lymph nodes, mesenteric lymph nodes, and Peyers patches. The data will allow for better understanding of the specialization of high endothelial venules (HEV) and their role in lymphocyte recruitment from the blood; the tissue-specific differentiation of lymphoid tissue vasculature; and the specialized features of capillary vs. post-capillary endothelium, including differences in signaling pathways, adhesive properties and mechanisms of hemostasis.
Publication Title
Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Drosophila melanogaster
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Poised RNA polymerase II changes over developmental time and prepares genes for future expression.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Murine ES cell gene expression before RA induction are used to compare gene expression for time-points of 8, 12, 16, 24, 36, 48, 60 and 72 hours post-induction.
Publication Title
Poised RNA polymerase II changes over developmental time and prepares genes for future expression.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples