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GSE11408
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Human cytomegalovirus induces a pro-inflammatory monocyte following infection. To begin to address how HCMV induces these rapid changes in infected monocytes, we examined the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of pro-inflammatory genes were upregulated within 4 hours post infection.
Publication Title
Transcriptome analysis reveals human cytomegalovirus reprograms monocyte differentiation toward an M1 macrophage.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 168 Downloadable Samples
Illumina HiSeq 2500
Description
Adult zebrafish are capable of regenerating cardiac tissue following ventricular resection within 30 days. We profiled both small RNA and mRNA expression in uninjured (0dpa), 1, 3, 7, 14, 21 and 30 days post amputation to study biological processes orchestrate each stage of regeneration. Overall design: Small and mRNA gene expression profiling during 0, 1, 3, 7, 14, 21 and 30 days post ventricular resection.
Publication Title
RegenDbase: a comparative database of noncoding RNA regulation of tissue regeneration circuits across multiple taxa.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The chronological lifespan (CLS) of Saccharomyces cerevisiae is defined as the number days that non-dividing cells remain viable, typically in stationary phase cultures or in water. CLS is extended by restricting glucose in the starting cultures, and is considered a form of caloric restriction (CR). Through a previous genetic screen our lab determined that deleting components of the de novo purine biosynthesis pathway also significantly increased CLS. Significant similarities in gene expression profiles between calorie restricted WT cells and a non-restricted ade4 mutant suggested the possibility of common gene expression biomarkers of all chronologically long lived cells that could also provide insights into general mechanisms of lifespan extension. We have identified additional growth conditions that extend CLS of WT cells, including supplementation of the media with isonicotinamide (INAM), a known sirtuin activator, or by supplementation with a concentrate collected from the expired media of a calorie restricted yeast culture, presumably due to an as yet unidentified longevity factor. Using these varied methods to extend CLS, we compared gene expression profiles in the aging cells (at day 8) to identify functionally relevant biomarkers of longevity. Nineteen genes were differentially regulated in all 4 of the long-lived populations relative to wild type. Of these 19 genes, viable haploid deletion mutants were available for 16 of them, and 12 were found to have a significant impact on CLS.
Publication Title
Functional genomic analysis reveals overlapping and distinct features of chronologically long-lived yeast populations.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In an effort to understand the mechanisms of acquired resistance to BRAF inhibitors, we isolated clones that acquired resistance to the BRAF inhibitor GSK2118436 derived from the A375 BRAF V600E mutant melanoma cell line. This resistance clones acquired mutations in NRAS and MEK1. One clones, 16R6-4, acquired two mutations in NRAS Q61K and A146T. Proliferation and western blot analyses demonstrated that these clones were insensitive to single agent GSK2118436 or GSK1120212 (an allosteric MEK inhibitor) but were sensitive to the combination of GSK2118436 and GSK1120212. To further characterize this combination, global transcriptomic analysis was performed in A375 and 16R6-4 after 24 hour treatment with GSK2118436, GSK1120212 or the combination of GSK2118436 and GSK1120212.
Publication Title
Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 282 Downloadable Samples
- Illumina HiSeq 2000
Description
Previous studies had shown that integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals both local and trans expression Quantitative Trait Loci (eQTLs) demonstrating 2 trans eQTL "hotspots" associated with expression of hundreds of genes. We also report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provides a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation. Overall design: 282 samples, 3 biological replicates per strain
Publication Title
Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes.
Sample Metadata Fields
Sex, Cell line, Subject
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HiSeq 2500
Description
We decribe the accessible chormatin landscape in RAS-induced (RIS) and NOTCH induced senescence (NIS) using ATAC-seq. By expressing active NOTCH (N1ICD) in the context of RIS, we find that N1ICD antagonises the formation of accessible regions in RIS. By performing co-cultures, we demonstrate that cells expressing a NOTCH1 ligand, JAGGED1, can antagonise the formation of RIS specific accessible regions. Overall design: mRNA profiles were IMR90 cells expressing ER:HRAS(G12V) and a control vector or MSCV miR30 shHMGA1 were generated. 6 biological replicates.
Publication Title
NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinsons disease (PD) are not completely understood. Here we use microarrays and mass spectrometry to study the transcriptomic and proteomic changes in the striatum of two mouse models of PD induced by distinct neurotoxins, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Transcripts and proteins were found with similar abundance changes in both models which may be involved in the pathophysiology of PD. GFAP transcript and protein levels were significantly up-regulated by both neurotoxins, confirming the known astrocytic response to these drugs. Other genes and proteins were idiosyncratic in their responses to the two toxins, suggesting specific toxicological responses. Comparing transcript and protein levels revealed that efficiently translated genes used more commonly occurring codons than inefficiently translated genes. Additionally, a potential role was found for miRNAs in translational control in the striatum. The results constitute one of the largest datasets integrating transcript and protein changes for these two neurotoxin models with many similar endpoint phenotypes but distinct pathologies. Using multiple toxins while examining proteins and transcripts can be an effective method of delineating the molecular pathology of neurodegenerative diseases.
Publication Title
Mitochondrial dysfunction, oxidative stress, and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson's disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 82 Downloadable Samples
- Illumina HiSeq 2500
Description
Combined treatment with all-trans retinoic acid and GSK2879552 results in synergistic effects on gene expression, cell proliferation, markers of differentiation, and, most importantly, cytotoxicity. Overall design: Gene expression analysis of DMSO, single and combination treatment (ATRA and GSK2879552) on 6 AML cell lines at two time-points with two replicates (paired end RNA-seq on 96 samples in total)
Publication Title
Lysine specific demethylase 1 inactivation enhances differentiation and promotes cytotoxic response when combined with all-<i>trans</i> retinoic acid in acute myeloid leukemia across subtypes.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 53 Downloadable Samples
- Illumina HiSeq 2500
Description
The meningeal space is occupied by a diverse repertoire of innate and adaptive immune cells. CNS injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation in CNS injury remains poorly understood. Here we describe group 2 innate lymphoid cells (ILC2s) as a novel cell type resident in the healthy meninges that is activated following CNS injury. ILC2s are present throughout the naïve mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile relative to lung ILC2s. After spinal cord injury, meningeal ILC2s are activated in an IL-33 dependent manner, producing type 2 cytokines. Using RNAseq, we characterized the gene programs that underlie the ILC2 activation state. Finally, addition of wild type lung-derived ILC2s into the meningeal space of IL-33R-/- animals improves recovery following spinal cord injury. These data characterize ILC2s as a novel meningeal cell type that responds to and functionally affects outcome after spinal cord injury, and could lead to new therapeutic insights for CNS injury or other neuroinflammatory conditions. Overall design: ILC2s were isolated from 10 week C57/Bl6 mice with and without spinal cord injury (1 day post injury). 5 mice were pooled per group, with meninges dissected, digested, and FACs sorted (CD45+/DAPI-/Lin–/St2+/Thy1+) directly into RNA lysis buffer.
Publication Title
Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Peptide immunotherapy aims to specifically restore tolerance to the administered self-antigen and prevent autoimmunity without the perturbation of normal immune function. We have developed a dose escalation protocol for subcutaneous delivery of the MHC II-restricted myelin basic protein peptide analogue Ac1-9[4Y] to T cell receptor transgenic (Tg4) mice. Dose escalation allows safe administration of high doses of peptide, which effectively induces antigen-specific tolerance and suppresses the development of experimental autoimmune encephalomyelitis, a model for the human condition multiple sclerosis. CD4+ T cells isolated from treated mice are anergic and suppressive in vitro and respond to stimulation by secretion of the immunoregulatory cytokine IL-10. To understand the molecular changes occurring throughout the course of dose-escalation immunotherapy, we undertook microarray analysis of CD4+ T cells at different the stages of treatment, using Tg4 Rag-1 deficient mice, which lack naturally occurring regulatory T cells and have a monoclonal CD4+ T cell population
Publication Title
Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy.
Sample Metadata Fields
Specimen part, Treatment
View Samples