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SRP127255
Mus musculus
12 Downloadable Samples
Illumina HiSeq 4000
Description
Definitive hematopoietic cells arise from hemogenic endothelium during mid-gestation, indicating a direct link between blood and the endothelial-lined vessels. We sought to determine whether mutations initiated in the hemogenic endothelium would yield hematopoietic abnormalities or malignancies. Here we demonstrate that transposon mutagenesis targeting endothelial cells in mice promotes the development of hematopoietic pathologies that are both myeloid and lymphoid in nature. Sequencing of the disrupted genes identified several previously recognized candidate cancer drivers and furthermore revealed that mutations in the lipid kinase Pi4ka can result in myeloid and erythroid dysfunction. Subsequent validation experiments showed that targeted inactivation of the Pi4ka catalytic domain or reduction in mRNA expression inhibited myeloid and erythroid cell differentiation in vitro and promoted anemia in vivo through a mechanism that includes, but it is not limited to deregulation of Akt signaling. Finally, we provide evidence linking PI4KAP2, previously considered a “pseudogene”, with human myeloid and erythroid leukemia. Overall design: mRNA transcriptional comparison between two pieces of spleen from three SBxVEC-Cre+ animals and three control animals to assess clonality of each spleen as a whole.
Publication Title
A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Caenorhabditis elegans
- 7 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Background: Differential gene expression specifies the highly diverse cell types that constitute the nervous system. With its sequenced genome and simple, well-defined neuroanatomy, the nematode C. elegans is a useful model system in which to correlate gene expression with neuron identity. The UNC-4 transcription factor is expressed in thirteen embryonic motor neurons where it specifies axonal morphology and synaptic function. These cells can be marked with an unc-4::GFP reporter transgene. Here we describe a powerful strategy, Micro-Array Profiling of C. elegans cells (MAPCeL), and confirm that this approach provides a comprehensive gene expression profile of unc-4::GFP motor neurons in vivo. Results: Fluorescence Activated Cell Sorting (FACS) was used to isolate unc-4::GFP neurons from primary cultures of C. elegans embryonic cells. Microarray experiments detected 6,217 unique transcripts of which ~1,000 are enriched in unc-4::GFP neurons relative to the average nematode embryonic cell. The reliability of these data was validated by the detection of known cell-specific transcripts and by expression in UNC-4 motor neurons of GFP reporters derived from the enriched data set. In addition to genes involved in neurotransmitter packaging and release, the microarray data include transcripts for receptors to a remarkably wide variety of signaling molecules. The added presence of a robust array of G-protein pathway components is indicative of complex and highly integrated mechanisms for modulating motor neuron activity. Over half of the enriched genes (537) have human homologs, a finding that could reflect substantial overlap with the gene expression repertoire of mammalian motor neurons.
Publication Title
A gene expression fingerprint of C. elegans embryonic motor neurons.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 2 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Transcriptome analysis of a population of wild type animals and lsm-1 mutants at L3 stage Overall design: lsm-1(tm3585) mutants were backcrossed three times with wild type N2 animals. lsm-1 mutants and N2 animals were grown for 26 hours at 25C from a synchronized L1 population.
Publication Title
Cytoplasmic LSM-1 protein regulates stress responses through the insulin/IGF-1 signaling pathway in Caenorhabditis elegans.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background & Aims: HNF4 is an important transcriptional regulator of hepatocyte and pancreatic function. Hnf4 deletion is embryonically lethal with severe defects in visceral endoderm formation, liver maturation and colon development. However, the precise role of this transcription factor in maintaining homeostasis of the adult intestine remains unclear. Herein, we aimed to elucidate the adult intestinal functions of Hnf4. Methods: A conditional intestinal epithelial Hnf4 knockout mouse was generated. Histological abnormality of the colonic mucosa was assessed by immunodetection and Western. Changes in global gene expression and biological network were analyzed. Results: Hnf4 intestine null mice developed normally until reaching young adulthood. Crypt distortion became apparent in the Hnf4 null colon at 3 months of age followed by focal areas of crypt dropout, increased immune cell infiltrates, crypt hyperplasia and early signs of polyposis later in life. A gene profiling analysis identified cell death and cell cycle related to cancer as the most significant sets of genes altered in the Hnf4 colon null mice. Expression levels of the tight junction proteins claudin 4, 8 and 15 were altered early in the colon epithelium of Hnf4 mutants and correlated with increased barrier permeability to a molecular tracer that does not normally penetrate normal mucosa. Conclusion: These observations support a functional role for Hnf4 in protecting the colonic mucosa against the initiation of the changes resembling inflammatory bowel diseases and polyp formation.
Publication Title
Loss of hepatocyte-nuclear-factor-4alpha affects colonic ion transport and causes chronic inflammation resembling inflammatory bowel disease in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neuromuscular disorder characterized by the selective degeneration of upper and lower motor neurons, progressive muscle wasting and paralysis. To define the full set of alterations in gene expression in skeletal muscle during the course of the disease, we performed high-density oligonucleotide microarray analysis of gene expression in hind limb skeletal muscles of sod1(G86R) mice, one of the existing transgenic models of ALS. To monitor denervation-dependent gene expression, we determined the effects of short-term acute denervation on the muscle transcriptome after sciatic nerve axotomy.
Publication Title
Gene profiling of skeletal muscle in an amyotrophic lateral sclerosis mouse model.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
We used microarrays to compare gene expression between shRNA targeting NRL and control replicates in D458Med cell line.
Publication Title
NRL and CRX Define Photoreceptor Identity and Reveal Subgroup-Specific Dependencies in Medulloblastoma.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Amyotrophic later sclerosis is a motor neuron disease accompanied by metabolic changes. PGC (PPAR gamma coactivator)-1alpha is a master regulator of mitochondrial biogenesis and function and of critical importance for all metabolically active tissues. PGC-1alpha is a genetic modifier of ALS.
Publication Title
ALS-causing mutations differentially affect PGC-1α expression and function in the brain vs. peripheral tissues.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Most cancer deaths are caused by metastases, which are the end-results of circulating tumor cells (CTC) that detach from the cancer primary and succeed to survive in distant organs. The aim of the present study was to develop a gene signature of CTC and to assess its prognostic relevance after surgery for pancreatic ductaladenocarcinoma (PDAC).
Publication Title
Pancreatic cancer circulating tumour cells express a cell motility gene signature that predicts survival after surgery.
Sample Metadata Fields
Sex, Age, Disease stage
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Following our initial transcriptomic analyses of the male gametophyte development (Honys and Twell, Genome Biol 5:R85, 2004), we identified several candidate genes for the function of transcriptional regulators of the male gametophyte development.
Publication Title
AtbZIP34 is required for Arabidopsis pollen wall patterning and the control of several metabolic pathways in developing pollen.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 15 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Domestic broiler chickens rapidly accumulate adipose tissue due to intensive genetic selection for rapid growth and are naturally hyperglycemic and insulin resistant, making them an attractive addition to the suite of rodent models used for studies of obesity and type 2 diabetes in humans. Furthermore, chicken adipose tissue is considered as poorly sensitive to insulin and lipolysis is under glucagon control. Excessive fat accumulation is also an economic and environmental concern for the broiler industry due to the loss of feed efficiency and excessive nitrogen wasting, as well as a negative trait for consumers who are increasingly conscious of dietary fat intake. Understanding the control of avian adipose tissue metabolism would both enhance the utility of chicken as a model organism for human obesity and insulin resistance and highlight new approaches to reduce fat deposition in commercial chickens.
Publication Title
Transcriptomic and metabolomic profiling of chicken adipose tissue in response to insulin neutralization and fasting.
Sample Metadata Fields
Specimen part
View Samples