Filters
Technology
Platform
SRP095733
Mus musculus
16 Downloadable Samples
Illumina HiSeq 2000
Description
Maintenance of vascular integrity in the adult animal is needed for survival and critically dependent on the endothelial lining, which controls barrier function, blood fluidity, and flow dynamics. However, nodal regulators that coordinate endothelial identity and function in the adult animal remain poorly characterized. Here we show that endothelial KLF2 and KLF4 control a large segment of the endothelial transcriptome thereby affecting virtually all key endothelial functions. Inducible endothelial-specific deletion of Klf2 and/or Klf4 reveals that a single allele of either gene is sufficient for survival, but absence of both (EC-DKO) results in acute death from myocardial infarction, heart failure, and stroke. EC-DKO animals exhibit profound compromise in vascular integrity and profound dysregulation of the coagulation system. Collectively, these studies establish an absolute requirement for KLF2/4 for maintenance of endothelial and vascular integrity in the adult animal. Overall design: Eight-to-ten-week old mice were intraperitoneally injected with tamoxifen to trigger endothelial-specific gene deletion of KLF2 and/or KLF4. At day 6 post-injection, endothelial cells were isolated from the heart and total RNA was purified.
Publication Title
KLF2 and KLF4 control endothelial identity and vascular integrity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
FVB mice were engineered to express wild-type human cyclin E under control of the human surfactant C promoter (CEO mice; Ma et al, PNAS 2007). These mice develop spontaneous lung tumors, which were shown to be adenocarcinoma by histological analysis. Here we compare whole-genome RNA expression levels between the tumors and normal lung of 4 CEO mice as well as 4 nontransgenic animals.
Publication Title
Evidence for tankyrases as antineoplastic targets in lung cancer.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Mitochondrial dysfunction has been directly or indirectly implicated in the pathogenesis of a number of neurodegenerative disorders including Parkinson's disease, Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS). We used exon-sentive microarrays to characterize the responses to different mitochondrial perturbations in cellular models. We examined human SH-SY5Y neuroblastoma cells treated with paraquat, a neurotoxic herbicide which both catalyzes the formation of reactive oxygen species (ROS) and induces mitochondrial damage in animal models, and SH-SY5Y cells stably expressing the mutant SOD1(G93A) protein, one of the genetic causes of ALS. We identified a common set of genes that have a deregulated transcription and alternative splicing in both models. Noticeably, pathway analysis revealed that the expression of a subset of genes involved in neuritogenesis and axon guidance is perturbed, suggesting that alterations of axonal function may descend directly from mitochondrial damage and be responsible for neurodegenerative conditions.
Publication Title
Mutant SOD1 and mitochondrial damage alter expression and splicing of genes controlling neuritogenesis in models of neurodegeneration.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Whole-genome profiling of SH-SY5Y cells was done on neuroblastoma SH-SY5Y stably transfected with cDNAs coding for SOD1WT or the mutant SOD1(G93A) protein.
Publication Title
Mutant SOD1 and mitochondrial damage alter expression and splicing of genes controlling neuritogenesis in models of neurodegeneration.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Human SH-SY5Y neuroblastoma cells treated with paraquat, a neurotoxic herbicide which both catalyzes the formation of reactive oxygen species (ROS) and induces mitochondrial damage in animal models was profiled using Affimetrix Exon 1.0 ST GeneChips
Publication Title
Mutant SOD1 and mitochondrial damage alter expression and splicing of genes controlling neuritogenesis in models of neurodegeneration.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
E-cadherin, a protein encoded by the CDH1 gene is the dominant epithelial cell adhesion molecule playing a crucial role in epithelial tissue polarity and structural integrity. The progression of 90% or more carcinomas is believed to be mediated by disruption of normal E-cadherin expression, subcellular localization or function. Despite the strong correlation between E-cadherin loss and malignancy the mechanism through how this occurs is not known in most sporadic and hereditary epithelial carcinomas. Previous works have shown the importance of CDH1 intron 2 sequences for proper gene and protein expression supporting the possibility of these being cis-modulators of E-cadherin expression/function. but when co-expressed it led to reduced cell-cell adhesiveness, increased invasion and angiogenesis. By expression array analysis, IFITM1 and IFI27 levels were found to be increased upon CDH1a overexpression. Importantly, CDH1a was found to be de novo expressed in gastric cancer cell lines when compared to normal stomach.
Publication Title
Transcription initiation arising from E-cadherin/CDH1 intron2: a novel protein isoform that increases gastric cancer cell invasion and angiogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1 year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study we have combined the analysis of a murine model and human samples of HCC to identify genes differentially expressed early in the process of hepatocarcinogenesis, using a microarray based approach. Expression of 190 genes was impaired in murine HCC from which 65 were further validated by low-density array RT PCR. The expression of the best 45 genes was then investigated in human samples resulting in 18 genes which expression was significantly modified in HCC. Among them, JUN, methionine adenosyltransferase 1A and 2A, phosphoglucomutase 1, and acyl CoA dehydrogenase short branched chain indicate defective cell proliferation as well as one carbon pathway, glucose and fatty acid metabolism, both in HCC and cirrhotic liver, a well known preneoplastic condition. These alterations were further confirmed in public transcriptomic datasets from other authors. In addition, vasodilator stimulated phosphoprotein, an actin-associated protein involved in cytoskeleton remodelling, was also found to be increased in the liver and serum of cirrhotic and HCC patients. In addition to revealing the impairment of central metabolic pathways for liver homeostasis, further studies may probe the potential value of the reported genes for the early detection of HCC.
Publication Title
A signature of six genes highlights defects on cell growth and specific metabolic pathways in murine and human hepatocellular carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Macaca mulatta
- 14 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Derivation of embryonic stem cells (ESC) genetically identical to a patient by somatic cell nuclear transfer (SCNT) holds the potential to cure or alleviate the symptoms of many degenerative diseases while circumventing any immunorejection issues. However, no primate nuclear transfer embryonic stem (ntES) cell lines have been derived to date. Here, we used a modified SCNT technique to produce rhesus macaque SCNT blastocysts at a relatively high efficiency from adult donor cells and we successfully derived two primate ntES cell lines from 304 oocytes (an overall efficiency of 0.7%). Nuclear and mitochondrial DNA analysis confirmed the ntES cell lines were derived from rhesus monkey SCNT blastocysts and both rhesus monkey ntES cell lines exhibited a normal ESC morphology, expressed key stemness markers, were transcriptionally indistinguishable from control ESC lines and differentiated into multiple cell types. This is, to our knowledge, the first confirmed derivation of primate ntES cell lines.
Publication Title
Producing primate embryonic stem cells by somatic cell nuclear transfer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
EKLF is a Krppel-like transcription factor identified as a transcriptional activator and chromatin modifier in erythroid cells. EKLF-deficient (Eklf -/-) mice die at day 14.5 of gestation from severe anemia. In this study, we demonstrate that early progenitor cells fail to undergo terminal erythroid differention in Eklf -/- embryos. To discover potential EKLF target genes responsible for the failure of erythropoiesis, transcriptional profiling was performed with RNA from wild type and Eklf -/- early erythroid progenitor cells. These analyses identified significant perturbation of a network of genes involved in cell cycle regulation, with the critical regulator of the cell cycle, E2f2, at a hub. E2f2 mRNA and protein levels were markedly decreased in Eklf -/- early erythroid progenitor cells, which showed a delay in the G1-to-S-phase transition. Chromatin immunoprecipitation analysis demonstrated EKLF occupancy at the proximal E2f2 promoter in vivo. Consistent with the role of EKLF as a chromatin modifier, EKLF binding-sites in the E2f2 promoter were located in a region of EKLF-dependent DNase I sensitivity in early erythroid progenitor cells. We propose a model in which EKLF-dependent activation and modification of the E2f2 locus is required for cell cycle progression preceding terminal erythroid differentiation.
Publication Title
Failure of terminal erythroid differentiation in EKLF-deficient mice is associated with cell cycle perturbation and reduced expression of E2F2.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Nimblegen human 16MB custom tiling array (HG17) design1, Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Properties of STAT1 and IRF1 enhancers and the influence of SNPs.
Sample Metadata Fields
Specimen part, Cell line
View Samples