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SRP051733
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2500
Description
Cohesinopathies are characterized by mutations in the cohesin complex. Mutations in NIPBL, a cohesin loader, result in Cornelia de Lange syndrome (CdLS). CdLS is a congenital genetic disorder distinguished by craniofacial dysmorphism, abnormal upper limb development, delayed growth, severe cognitive retardation, and multiple organ malformations.It has been suggested that CdLS is caused by defects in the cohesin network that alter gene expression and genome organization. However, the precise molecular etiology of CdLS is largely unclear. To gain insights, we sequenced mRNAs isolated from mouse embryonic fibroblasts of both WT and NIPBL-haploinsufficient mice and compared their transcriptomes. Overall design: Examination of gene expression of WT and NIPBL+/- mice by RNA-seq
Publication Title
NIPBL Controls RNA Biogenesis to Prevent Activation of the Stress Kinase PKR.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
Diesel exhaust (DE) has been shown to enhance allergic sensitization in animals following high dose instillation or chronic inhalation exposure scenarios. The purpose of this study was to determine if short term exposures to diluted DE enhance allergic immune responses to antigen, and identify possible mechanisms using microarray technology. BALB/c mice were exposed to filtered air or diluted DE to yield particle concentrations of 500 or 2000 g/m3 4 hr/day on days 0-4. Mice were sensitized intranasally with ovalbumin (OVA) antigen or saline on days 0-2, and 18 and all were challenged with OVA on day 28. Mice were necropsied either 4 hrs after the last DE exposure on day 4, or 18, 48, and 96 hrs after challenge. Immunological endpoints included OVA-specific serum IgE, biochemical and cellular profiles of bronchoalveolar lavage (BAL), and cytokine production in the BAL. OVA-sensitized mice exposed to both concentrations of DE had increased eosinophils, neutrophils, lymphocytes, and IL-6 post-challenge compared to OVA control, while DE/saline exposure yielded increases in neutrophils at the high dose only. Microarray analysis demonstrated distinct gene expression profiles for the high dose DE/OVA and DE/saline groups. DE/OVA induced pathways involved in oxidative stress and metabolism while DE in the absence of allergen sensitization modulated cell cycle control, growth and differentiation, G-proteins, and cell adhesion pathways. This study shows for the first time early changes in gene expression induced by the combination of diesel exhaust inhalation and antigen sensitization, which resulted in stronger development of an allergic asthma phenotype.
Publication Title
Increased transcription of immune and metabolic pathways in naive and allergic mice exposed to diesel exhaust.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
DEP exposure is linked to increases in cardiovascular effects. This effect is enhanced in individuals with pre-existing disease. Animal models of cardiovascular disease are used to study this susceptibility. The heart is rich in mitochondria, which produce high levels of free radicals, leading to inactivation of tricarboxylic acid cycle enzymes. We hypothesized that a 4-wk DEP inhalation would result in strain-related structural impairment of cardiac mitochondria and changes in these enzyme activities in WKY and SHR. Male rats (12-14 wks age) were exposed whole body to air or 0.5 or 2.0 mg/m3 DEP for 6h/d, 5 d/wk for 4 wks. Neutrophilic influx was noted in the bronchoalveolar lavage fluid in both strains. A slightly lower level of baseline cardiac mitochondrial aconitase activity was seen in SHR than WKY. Aconitase activity appeared to be decreased in an exposure related manner in both strains. Significantly higher baseline levels of cardiac cytosolic ferritin and aconitase activity were seen in the SHR than WKY. No exposure-related changes were noted in either of these measures. Mitochondrial succinate and isocitrate dehydrogenase activities were not changed following DEP exposure in either strain. Transmission electron microscopy images of the heart indicated abnormalities in cardiac mitochondria of control SHR but not control WKY. No exposure related ultrastructural changes were induced by DEP in either strain. In conclusion, strain differences in cardiac biomarkers of oxidative stress and structure of mitochondria exist between SHR and WKY. DEP exposure results in small changes in cardiac mitochondrial and cytosolic markers of oxidative stress. (Abstract does not represent USEPA policy.)
Publication Title
One-month diesel exhaust inhalation produces hypertensive gene expression pattern in healthy rats.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The Cohesin apparatus has a canonical role in sister chromatid cohesion. Heterozygous mutations in Nipped B-like (NIPBL), SMC1A, and SMC3 have been found in 60% of probands with Cornelia de Lange Syndrome (CdLS), a dominant multi-system genetic disorder with variable expression. We have performed a genome-wide transcription assessment as well as cohesin binding analysis using human lymphoblastoid cell lines (LCLs) from probands with CdLS and controls. Here, we report a unique profile of genes dysregulated in CdLS that correlates with different clinical presentations. Genome-wide analysis of cohesin binding demonstrates a preference for intergenic regions suggesting a cis-regulatory function mimicking that of an insulator. However, the binding sites are enriched within the promoter regions of the dysregulated genes and are significantly decreased in CdLS probands, indicating an alternative role of cohesin as a classic transcription factor. Cohesin also co-localizes with CTCF at the boundary elements affecting neighboring gene expression in CdLS probands. We propose that the CdLS phenotype is the result of dysregulated gene expression rather than defective sister chromatid cohesion. Phenotype specific expression profiles are also described.
Publication Title
Transcriptional dysregulation in NIPBL and cohesin mutant human cells.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
CHOPS syndrome is caused by germline gain-of-function mutations of AFF4. Cornelia de Lange syndrome is caused by germline mutations of cohesin loading factors or cohesin complex genes such as NIPBL, SMC1A, SMC3 and HDAC8. There are many overlapping clinical features exist between CHOPS syndrome and Cornelia de Lange syndrome. To identified commonly dysregulated genes in CHOPS syndrome and Cornelia de Lange syndrome, we perfomred side-by-side transcriptome comparison between CHOPS syndrome and Cornelia de Lange syndrome.
Publication Title
Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
AFF4 is a component of super elongation complex (SEC), which plays an important role in mobilizing paused RNA polymerase II at gene promoter regions. Using exome sequenging, we have identified a novel genetic disorder caused by missense mutations in AFF4. We propose CHOPS syndrome as a name for this new diagnosis. To evaluate the effect of identified missense mutations of AFF4, utilizing patient derived skin fibroblast cell lines, the gene expression analysis was perfomred.
Publication Title
Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Maternal smoking doubles the risk of delivering a low birth weight infant. The purpose of this study was to analyze differential gene expression in umbilical cord tissue as a function of maternal smoking, with an emphasis on growth-related genes. We recruited 15 pregnant smokers and 15 women who never smoked during pregnancy to participate RNA was isolated from umbilical cord tissue collected and snap frozen at the time of delivery. Microarray analysis was performed using the Affymetrix GeneChip Scanner 3000.Six hundred seventy-eight probes corresponding to 545 genes were differentially expressed (i.e., an intensity ratio that exceeded +/-1.3 and a corrected significance value p < 0.005) in tissue obtained from smokers versus nonsmokers. Genes important for fetal growth, angiogenesis, or development of connective tissue matrix were up-regulated among smokers. The most highly up-regulated gene was CSH1, a somatomammotropin gene. Two other somatomammotropin genes (CSH2 and CSH-L1) were also up-regulated. The most highly down-regulated gene was APOBEC3A; other down-regulated genes included those that may be important in immune and barrier protection. PCR validation of the three somatomammotropin genes showed a high correlation between qPCR and microarray expression. Consequently, maternal smoking may be associated with altered gene expression in the offspring.
Publication Title
Effects of prenatal tobacco exposure on gene expression profiling in umbilical cord tissue.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Clariom S Pico Assay HT (clariomshumanht)
Description
Human ILCs are classically categorized into five subsets; cytotoxic CD127-CD94+ NK cells and non-cytotoxic CD127+CD94-, ILC1s, ILC2s, ILC3s and LTi cells. Here, we identify a novel subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs strongly resemble conventional ILC3s in terms of phenotype, transcriptome and cytokine production, but are highly cytotoxic. IL-15 was unable to induce differentiation of CD94+ ILCs towards mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic CD127+ ILC1s or ILC3s with IL-12 induced upregulation of CD94 and cytotoxic activity, effects that were not observed with IL-15 stimulation. Thus, human helper ILCs can acquire a cytotoxic program without differentiating into NK cells.
Publication Title
Identification of human cytotoxic ILC3s.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Proteinases play a pivotal role in wound healing by degrading molecular barriers, regulating cell-matrix interactions and availability of bioactive molecules. Matrix metalloproteinase-13 (MMP-13, collagenase-3) is a wide spectrum proteinase. Its expression and function is linked to the growth and invasion of many epithelial cancers such as squamous cell carcinoma. Moreover, the physiologic expression of MMP-13 is associated e.g. to scarless healing of human fetal skin and adult gingival wounds. While MMP-13 is not found in the normally healing skin wounds in human adults, it is expressed in mouse skin during wound healing. Thus, mouse wound healing models can be utilized for studying the role of MMP-13 in the events of wound healing. As the processes such as the migration and proliferation of keratinocytes, angiogenesis, inflammation and activation of fibroblasts are components of wound repair as well as of cancer, many results received from wound healing studies are also adaptable to cancer research.
Publication Title
MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.
Sample Metadata Fields
Time
View Samples- Rattus norvegicus
- 26 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5-6 months, middle-aged F344 rats were fed diets containing low, medium (typical amount) or high vitamin D3 (100, 1000 or 10,000 IU/kg diet, respectively) and then hippocampal-dependent learning and memory were tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication and G-protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function and suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging.
Publication Title
Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats.
Sample Metadata Fields
Sex, Specimen part
View Samples