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GSE48911
Mus musculus
31 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Glud1 (Glutamate dehydrogenase 1) transgenic mice release more excitatory neurotransmitter glutamate to synaptic cleft throughout lifespan.
Publication Title
Gene expression patterns in the hippocampus during the development and aging of Glud1 (Glutamate Dehydrogenase 1) transgenic and wild type mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Mesenchyme-derived cells in the human airway wall including airway smooth muscle cells, fibroblasts and myofibroblasts are known to play important roles in airway remodeling. The lack of specific phenotypic markers makes it difficult to define these cell populations in primary cultures. The objectives of this study were to evaluate reported markers and to identify novel markers to define these cell types.
Publication Title
Can lineage-specific markers be identified to characterize mesenchyme-derived cell populations in the human airways?
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Tyrosine kinase inhibitors (TKIs), despite efficacy as anti-cancer therapies, are associated with cardiovascular side effects ranging from induced arrhythmias to heart failure. We have utilized patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), generated from 11 healthy individuals and 2 patients receiving cancer treatment, to screen FDA-approved TKIs for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling. With these data, we generated a cardiac safety index to assess cardiotoxicities of existing TKIs. Many TKIs with a low cardiac safety index exhibit cardiotoxicity in patients. We also derived endothelial cells (hiPSC-ECs) and cardiac fibroblasts (hiPSC-CFs) to examine cell type-specific cardiotoxicities. Using high-throughput screening, we determined that VEGFR2/PDGFR-inhibiting TKIs caused cardiotoxicity in hiPSC-CMs, hiPSC-ECs, and hiPSC-CFs. Using phosphoprotein analysis, we determined that VEGFR2/PDGFR-inhibiting TKIs led to a compensatory increase in cardioprotective insulin and insulin-like growth factor (IGF) signaling in hiPSC-CMs. Activating cardioprotective signaling with exogenous insulin or IGF1 improved hiPSC-CM viability during co-treatment with cardiotoxic VEGFR2/PDGFR-inhibiting TKIs. Thus, hiPSC-CMs can be used to screen for cardiovascular toxicities associated with anti-cancer TKIs, correlating with clinical phenotypes. This approach provides unexpected insights, as illustrated by our finding that toxicity can be alleviated via cardioprotective insulin/IGF signaling.
Publication Title
High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 29 Downloadable Samples
Illumina HiSeq 2500
Description
Translating ribosome affinity purification technology was used to isolate mRNAs from cerebellar Purkinje neurons from control (Pcp2-BacTrap; Rbm17 f/+) and mutant (Pcp2-BacTRAP; Pcp2-Cre; Rbm17 f/-) mice. Overall design: RNA isolation was performed when animals were four-weeks-old (n=3 animals per genotype). Using NuGEN Ovation RNA-Seq System v2, purified double-stranded cDNA was generated from 10 ng of total RNA and amplified using both 3' poly (A) selection and random priming. 2 µg of each sample was sheared using the Covaris S2 focused-ultrasonicator following the manufacturer's protocol to obtain a final library with insert size of 400 bp. The sheared samples were quantified using the NanoDrop ND-1000 spectrophotometer and Invitrogen Qubit 2.0 DNA quantitation assay. The fragment sizes were confirmed on the Agilent Bioanalyzer to verify proper shearing. A double-stranded DNA library was produced using Illumina TruSeq DNA library preparation system and the sequencing was run on a HiSeq 2500 system.
Publication Title
Extensive cryptic splicing upon loss of RBM17 and TDP43 in neurodegeneration models.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchips
Description
Human clinical trials in type 1 diabetes (T1D) patients are underway using mesenchymal stem cells (MSC) without prior validation in a mouse model for the disease. In response to this void, we characterized bone marrow-derived murine MSC for their ability to modulate immune responses in the context of T1D, as represented in non-obese diabetic (NOD) mice. In comparison to NOD-, BALB/c-MSC express higher levels of the negative costimulatory molecule PD-L1 and promote a shift toward Th2-like responses in treated NOD mice. In addition, transfer of MSC from resistant strains (i.e. NOR or BALB/c), but not from NOD mice, conferred disease protection when administered to prediabetic NOD mice. The number of BALB/c-MSC trafficking to the pancreatic lymph nodes of NOD mice was higher than in NOD mice provided autologous NOD-MSC. Administration of BALB/c-MSC resulted in reversal of hyperglycemia in 90% of NOD mice (p=0.002). Transfer of autologous NOD-MSC imparted no such therapeutic benefit, and in fact soft tissue and visceral tumors were uniquely observed in this setting (i.e. no tumors were present with BALB/c- or NOR-MSC transfer). These data provide important preclinical data supporting the basis for further development of allogeneic MSC-based therapies for T1D and potentially, other autoimmune disorders.
Publication Title
Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Benign prostatic hyperplasia (BPH) is a common urological disease that adversely affects quality of life among elderly males, but its etiology remains poorly understood. We show that the expression of the androgen receptor (AR) is decreased in the luminal epithelial cells of human BPH specimens and is inversely correlated with the degree of regional prostatic inflammation. Overall design: To identify the extracellular signaling that promotes epithelial proliferation, we performed RNA sequencing of FACS-isolated prostate luminal cells from tamoxifen-treated control and K8-AR mice (with knockout of androgen receptor).
Publication Title
Non-Cell-Autonomous Regulation of Prostate Epithelial Homeostasis by Androgen Receptor.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Essential fatty acids (FA) are not only energy-rich molecules; they are also an important component of the membrane bilayer and recently have been implicated in induction of fatty acid synthase (FAS) and other genes. Using gene chip analysis, we have found that arachidonic acid (AA), an omega-6 fatty acid, induced 11 genes that are regulated by NFkappaB. We verified gene induction by omega-6 fatty acids including COX2, IKBA, NFKB, GMCSF, IL1B, CXCL1, TNFA, IL6, LTA, IL8, PPARG, and ICAM1 using qRTPCR. PGE2 synthesis was increased within 5min of addition of AA. Analysis of upstream signal transduction showed that within 5min of FA addition, phophatidylinositol 3-kinase (PI3K) was significantly activated followed by activation of Akt at 30min. ERK1 and 2, p38, and SAPK/JNK were not phosphorylated after omega-6 FA addition. Thirty minutes after FA addition, we found a significant 3-fold increase in translocation of NFkappaB transcription factor to the nucleus. Addition of non-steroidal anti-inflammatory drug (NSAID) caused a decrease in cox-2 protein synthesis, PGE2 synthesis as well as inhibition of PI3K activation. We have previously shown that AA induced proliferation is also blocked (P<0.001) by PI3K inhibitor LY294002. LY294002 also significantly inhibited the AA induced gene expression of COX2, IL1B, GMCSF, and ICAM1. Taken together, the data suggests that AA via conversion to PGE2 plays an important role in stimulation of growth related genes and proliferation via PI3K signaling and NFkappaB translocation to the nucleus.
Publication Title
Arachidonic acid activates phosphatidylinositol 3-kinase signaling and induces gene expression in prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Mediator is regarded a general co-activator of RNA-Polymerase II dependent transcription but not much is known about its function and regulation in mouse pluripotent embryonic stem cells (mESC). One means of controlling Mediator function is provided by binding of the Cdk8 module (Med12, Cdk8, Ccnc and Med13) to Mediator. Here we report that the Cdk8 module subunit Med12 operates together with PRC1 to silence developmental key genes in the pluripotent state. At the molecular level, PRC1 is required to assemble ncRNA containing Med12-Mediator complexes at promoters of repressed genes. In the course of cellular differentiation the H2A-ubiquitin binding protein Zrf1 abrogates PRC1-Med12 binding and facilitates the recruitment of Cdk8 into Mediator. Remodeling of the Mediator-associated protein complex converts Mediator into a transcriptional enhancer that mediates ncRNA-dependent activation of Polycomb target genes Overall design: RNAseq of pluripotent (control, shNMC, shRing1b, shMed12, shCdk8, shZrf1) and early differentiating (control, shNMC, shMed12, shCdk8, shZrf1) stem cells in triplicates. Control would be normal E14TG2A mESCs. shNMC refers to E14TG2A cells stably transfected with a short hairpin that has no mammalian targets (Non Mammalian Control). All the other samples are indeed stably transfected with short hairpins against the indicated genes.
Publication Title
Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Danio rerio
- 15 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Pharmaceutical chemicals used in human medicine are released into surface waters via municipal effluents and pose a risk for aquatic organisms. Among these substances are selective serotonin reuptake inhibitors (SSRIs) which can affect aquatic organisms at sub ppb concentrations. To better understand biochemical pathways influenced by SSRIs, evaluate changes in the transcriptome, and identify gene transcripts with potential for biomarkers of exposure to SSRIs; larval zebrafish Danio rerio were exposed (96 h) to two concentrations (25 and 250 g/L) of the SSRIs, fluoxetine and sertraline, and changes in global gene expression were evaluated (Affymetrix GeneChip Zebrafish Array). Significant changes in gene expression (>=1.7 fold change, p<0.05) were determined with Partek Genomics Suite Gene Expression Data Analysis System and ontology analysis was conducted using Molecular Annotation System 3. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 g/L and 131 at 250 g/L; and after sertraline exposure was 33 at 25 g/L and 52 at 250 g/L. Five genes were differentially regulated in all treatments relative to control, suggesting that both SSRIs share some similar molecular pathways. Among them, expression of the gene coding for FK506 binding protein 5 (FKBP5), which is annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated that regulation of stress response and cholinesterase activity were critical functions influenced by these SSRIs, and suggested that changes in the transcription of FKBP5 or acetylcholinesterase could be useful biomarkers of SSRIs exposure in wild fish.
Publication Title
Global gene expression in larval zebrafish (Danio rerio) exposed to selective serotonin reuptake inhibitors (fluoxetine and sertraline) reveals unique expression profiles and potential biomarkers of exposure.
Sample Metadata Fields
No sample metadata fields
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