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GSE110031
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
These data show that Paupar, a CNS expressed long non-coding RNA (lncRNA), directly and functionally associates with KAP1, an essential epigenetic regulatory protein. Transcriptome profiling of N2A cells identified 1,913 differentially expressed genes whose expression significantly changed (at a 5% false discovery rate [FDR]) greater than 1.4-fold (log2 fold change 0.5) upon KAP1 depletion. Examination of the intersection of KAP1 and Paupar transcriptional targets showed that Paupar and KAP1 control expression of a shared set of target genes that are enriched for regulators of neuronal function and cell cycle in N2A cells. Furthermore, CHART-seq and ChIP-seq derived Paupar-KAP1 genome-wide co-occupancy maps revealed a 4-fold enrichment of overlap between Paupar and KAP1 bound sequences on chromatin. This study also indicates that Paupar promotes KAP1 chromatin occupancy and H3K9me3 deposition at a subset of distal targets, through formation of a ribonucleoprotein complex containing Paupar, KAP1 and the PAX6 transcription factor. These observations provide important conceptual insights into the trans-acting modes of lncRNA-mediated epigenetic regulation and the mechanisms of KAP1 genomic recruitment.
Publication Title
The long non-coding RNA <i>Paupar</i> promotes KAP1-dependent chromatin changes and regulates olfactory bulb neurogenesis.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The long non-coding RNA <i>Paupar</i> promotes KAP1-dependent chromatin changes and regulates olfactory bulb neurogenesis.
Sample Metadata Fields
Cell line
View Samples- Macaca mulatta
- 64 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure.
Sample Metadata Fields
Specimen part
View Samples- Macaca mulatta
- 34 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
The SIVmac251 macaque model has been used to evaluate the efficacy of vaccine for HIV. Exposure of macaques to a single high dose of SIVmac251 results in transmission of multiple viral variants, which contrasts the few HIV variants typically transmitted in humans. In here, we investigated whether the dose of SIVmac251 challenge affected vaccination efficacy and found that exposure of the immunized macaques to single high dose of SIVmac251 resulted in no vaccine efficacy, whereas exposure to a tenfold lower dose resulted in protection from SIVmac251 acquisition and protection from disease in animals that become infected. The dose of challenge did not affect the expression of inflammatory genes in the gut in acute infection, but at set point, a significant down regulation of interferon responsive genes and up regulation of genes involved in B and T-cell responses, was observed only in vaccinated animals exposed to a lower dose of SIVmac251. Accordingly, in these animals, we also found a significant correlation with vaccine induced T-cell responses and protection from disease. These data demonstrate that the evaluation of the efficacy of vaccine candidates for HIV relies on accurate modeling in macaques to better mimic HIV transmission to humans.
Publication Title
Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure.
Sample Metadata Fields
Specimen part
View Samples- Macaca mulatta
- 30 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
The SIVmac251 macaque model has been used to evaluate the efficacy of vaccine for HIV. Exposure of macaques to a single high dose of SIVmac251 results in transmission of multiple viral variants, which contrasts the few HIV variants typically transmitted in humans. In here, we investigated whether the dose of SIVmac251 challenge affected vaccination efficacy and found that exposure of the immunized macaques to single high dose of SIVmac251 resulted in no vaccine efficacy, whereas exposure to a tenfold lower dose resulted in protection from SIVmac251 acquisition and protection from disease in animals that become infected. The dose of challenge did not affect the expression of inflammatory genes in the gut in acute infection, but at set point, a significant down regulation of interferon responsive genes and up regulation of genes involved in B and T-cell responses, was observed only in vaccinated animals exposed to a lower dose of SIVmac251. Accordingly, in these animals, we also found a significant correlation with vaccine induced T-cell responses and protection from disease. These data demonstrate that the evaluation of the efficacy of vaccine candidates for HIV relies on accurate modeling in macaques to better mimic HIV transmission to humans.
Publication Title
Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Like humans, the NOD mouse and other diabetes susceptible rat strains, T1D in BB rats is dependent on the major histocompatibility complex (MHC, insulin dependent diabetes mellitus locus 1, Iddm1) located on chromosome 20. In rats this is the HLA-DQB1 homologue RT1-B, specifically the RT1u haplotype. Our studies employ congenic derivatives of the BB rat, the DRlyp/lyp and DR+/+ strains, which differ only by the 2 Mb lyp (lymphopenia, Iddm2) region on chromosome 4. TID in the lymphopenic DRlyp/lyp rat is spontaneous and onset occurs in 100% of animals during adolescence (65.3+/-6.3 days) due to a recessive mutation within GIMAP5 (GTPase, IMAP family member 5). Gimap5 is a mitochondrial GTP-binding protein necessary for post-thymic T cell survival. The spontaneously diabetic phenotype observed in DRlyp/lyp rats is thought to be elicited through deficiency in CD4+CD25+ TREG cells as T1D in lymphopenic BB rats can be rescued through adoptive transfer of this population. Genetic variation in GIMAP5 has been associated with the development of protein-tyrosine phosphatase-2 (IA-2) autoantibodies in human T1D [28] and is significantly associated with systemic lupus erythematosus (SLE). The non-lymphopenic DR+/+ strain possesses wild-type GIMAP5 alleles and does not develop spontaneous T1D, however, T1D is inducible through administration of lymphotoxic anti-RT6 monoclonal antibody and immune activating polyinosinic polycytidylic acid (poly I:C; a ligand of toll-like receptor 3), or through viral depletion of CD4+CD25+ regulatory T (TREG) cells. Such treatments do not induce T1D in the related Wistar-Furth (WF) rats and suggest the presence of an underlying diabetic predisposition in BB rats that is phenotypically manifested upon loss of immune regulation.
Publication Title
Biobreeding rat islets exhibit reduced antioxidative defense and N-acetyl cysteine treatment delays type 1 diabetes.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Diabetic embryopathy can affect any developing organ system, although cardiovascular malformations, neural tube defects and caudal dysgenesis syndrome are the most prominent congenital malformations. We hypothesize that the metabolic imbalance occurring in diabetic pregnancy de-regulates tissue specific gene expression programs in the developing embryo. In order to identify genes whose expression is affected by maternal diabetes, we analyzed gene expression profiles of diabetes-exposed mouse embryos by using Affymetrix microarrays. We identified 129 genes with altered expression levels; 21 genes had increased and 108 genes had decreased expression levels in diabetes-exposed embryos relative to controls. A substantial fraction of these genes (35) are essential for normal embryonic development as shown by functional studies in mouse models. The largest fraction of diabetes-affected genes was in transcription factor and DNA-binding/chromatin remodeling functional categories (19%), which directly affect transcription. These findings suggest that transcriptional regulation in the developing embryos is perturbed by maternal diabetes and that transcriptional regulation plays a major role in the responses of embryos to intrauterine exposure to diabetic conditions. Interestingly, we found the expression of hypoxia-inducible factor 1 (Hif1) deregulated in the embryos exposed to the conditions of maternal diabetes. Since hypoxic stress is associated with the complications of diabetic pregnancy, we performed a post-hoc analysis of our microarray data with a specific focus on known HIF1 target genes. Of 39 genes detected in our microarrays, the expression changes of 22 genes (20 were increased and two genes were decreased in diabetes-exposed embryos) were statistically significant. These results indicate that HIF1-regulated pathways are affected in diabetes-exposed embryos. These results strongly suggest that de-regulation of hypoxia/HIF1 activated pathways could be the one of the key molecular events associated with the exposure to the teratogenic intrauterine environment of a diabetic mother.
Publication Title
Maternal diabetes alters transcriptional programs in the developing embryo.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Exposure to maternal diabetes during pregnancy alters transcriptional profiles in the developing embryo. The enrichment, within the set of de-regulated genes, of those encoding transcriptional regulatory molecules provides support for the hypothesis that maternal diabetes affects specific developmental programs.
Publication Title
Maternal diabetes alters transcriptional programs in the developing embryo.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 202 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 114 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D and HC cohorts. In addition, we examined T1D progression by looking at longitudinal, pre-onset and longstanding T1D samples.
Publication Title
Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples