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GSE58368
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover a striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype.
Publication Title
Notch signaling functions in retinal pericyte survival.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 562 Downloadable Samples
Illumina HiSeq 2500
Description
RNA-seq experiment on five mouse brain regions-- --comparing expression in virgin females to primiparous females three weeks after pup weaning. For each brain region there are 8 replicates, though three samples were not used in the final analysis based on inspection of PCA plots (1 sample from the Hippocampus, Cerebellum and Amygdala data sets; see details below). Overall design: Comparison of gene expression in five brain regions between eight virgin and eight primiparous females three weeks after pup weaning. Pair-wise comparisons were performed using EdgeR transformed data and Limma Voom for statistical analysis.
Publication Title
Maternal Experience Leads to Lasting Gene Expression Changes in Some Regions of the Mouse Brain.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To investigate whether and how expression of the oncogenic transcription factor EVI1 influences gene regulation by phorbol esters and vice versa, the human myeloid cell line U937 was transduced with an EVI1 expression vector or empty vector as a control. Cells were treated with 12-Otetradecanoylphorbol 13-acetate (TPA) or its solvent ethanol as a control. RNA was extracted and subjected to gene expression microarray analysis.
Publication Title
The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The product of the ecotropic virus integration site 1 (EVI1) gene, whose overexpression is associated with a poor prognosis in myeloid leukemias and some epithelial tumors, regulates gene transcription both through direct DNA binding and through modulation of the activity of other sequence specific transcription factors. Previous results from our laboratory have shown that EVI1 influenced transcription regulation in response to the myeloid differentiation inducing agent, all-trans retinoic acid (ATRA), in a dual manner: it enhanced ATRA induced transcription of the RARb gene, but repressed the ATRA induction of the EVI1 gene itself. In the present study, we asked whether EVI1 would modulate the ATRA regulation of a larger number of genes, as well as biological responses to this agent, in human myeloid cells. U937 and HL-60 cells ectopically expressing EVI1 through retroviral transduction were subjected to microarray based gene expression analysis, and to assays measuring cellular proliferation, differentiation, and apoptosis. These experiments showed that EVI1 modulated the ATRA response of several dozens of genes, and in fact reinforced it in the vast majority of cases. A particularly strong synergy between EVI1 and ATRA was observed for GDF15, which codes for a member of the TGF-b superfamily of cytokines. In line with the gene expression results, EVI1 enhanced cell cycle arrest, differentiation, and apoptosis in response to ATRA, and knockdown of GDF15 counteracted some of these effects.
Publication Title
The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The product of the ecotropic virus integration site 1 (EVI1) gene, whose overexpression is associated with a poor prognosis in myeloid leukemias and some epithelial tumors, regulates gene transcription both through direct DNA binding and through modulation of the activity of other sequence specific transcription factors. Previous results from our laboratory have shown that EVI1 influenced transcription regulation in response to the myeloid differentiation inducing agent, all-trans retinoic acid (ATRA), in a dual manner: it enhanced ATRA induced transcription of the RARb gene, but repressed the ATRA induction of the EVI1 gene itself. In the present study, we asked whether EVI1 would modulate the ATRA regulation of a larger number of genes, as well as biological responses to this agent, in human myeloid cells. U937 and HL-60 cells ectopically expressing EVI1 through retroviral transduction were subjected to microarray based gene expression analysis, and to assays measuring cellular proliferation, differentiation, and apoptosis. These experiments showed that EVI1 modulated the ATRA response of several dozens of genes, and in fact reinforced it in the vast majority of cases. A particularly strong synergy between EVI1 and ATRA was observed for GDF15, which codes for a member of the TGF-b superfamily of cytokines. In line with the gene expression results, EVI1 enhanced cell cycle arrest, differentiation, and apoptosis in response to ATRA, and knockdown of GDF15 counteracted some of these effects.
Publication Title
The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Airway basal cells (BC) function as progenitor cells capable of differentiating into ciliated and secretory cells to replenish the airway epithelium during physiological turnover and repair. The objective of this study was to define the role of Notch signaling in regulating human airway BC differentiation into a pseudostratified mucociliated epithelium. Notch inhibition with -secretase inhibitors demonstrated Notch activation is essential for BC differentiation into secre-tory cells and ciliated cells, but more so for the secretory lineage. Sustained Notch activation via lentivirus expression of the intracellular domain of each Notch receptor (NICD1-4) demonstrated that the Notch 2 and 4 pathways have little effect on BC differentiation, while activation of the Notch1 or 3 pathways has a major influence, with persistent expression of NICD1 or 3 resulting in a skewing toward secretory cell differentiation with a parallel decrease in ciliated cell differentiation. These observations provide insights into the control of the balance of BC differentiation into the secretory vs ciliated cell lineage, a balance that is critical for maintaining the normal function of the airway epithelium in barrier defense against the inhaled environment.
Publication Title
Activation of NOTCH1 or NOTCH3 signaling skews human airway basal cell differentiation toward a secretory pathway.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 38 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transcriptional analysis of identified DRG subpopulations.
Publication Title
Scaling proprioceptor gene transcription by retrograde NT3 signaling.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 38 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Drosophila melanogaster adult males perform an elaborate courtship ritual to entice females to mate. fruitless (fru), a gene that is one of the key regulators of male courtship behavior, encodes multiple male-specific isoforms (FruM). These isoforms vary in their carboxy-terminal zinc finger domains, which are predicted to facilitate DNA binding. By over-expressing individual FruM isoforms in fru-expressing neurons in either males or females and assaying the global transcriptional response by RNA-sequencing, we show that three FruM isoforms have different regulatory activities that depend on the sex of the fly. We identified several sets of genes regulated downstream of FruM isoforms. Overall design: RNA seqeuncing was performed on mRNA derived from adult male or female heads, for a total of 39 samples. These samples included two wild type genotypes (Berlin and Canton-S), two transheterozygous mutants for fru P1 (Df(3R)P14/Df(3R)fru4-40 and fruw12/ Df(3R)ChaM5), and 3 overexpressing genotypes (fru P1-Gal4: UAS-FruMA, UAS-FruMB, UAS-FruMC). There were at least 3 replicates from biological samples for all sex by genotype combinations.
Publication Title
Sex Differences in Drosophila Somatic Gene Expression: Variation and Regulation by doublesex.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 34 Downloadable Samples
- Illumina HiSeq 2500
Description
Identifying sex differences in gene expression within the brain is critical for determining why multiple neurological and behavioral disorders differentially affect males and females. Several are more common or severe in males (e.g., autism and schizophrenia) or females (e.g., Alzheimer’s disease and depression). We analyzed transcriptomic data from the mouse hippocampus of six inbred strains (129S1/SvImJ, A/J, C57BL/6J, DBA/1J, DBA/2J and PWD/Ph), to provide a perspective on differences between male and female gene expression. Our data show that: 1) significant gene expression differences in males versus females varies substantially across the strains, 2) 12 genes exist that are differentially expressed across the inbred strains (termed core genes), and 3) there are >2,600 significantly differentially expressed genes (DEGs) among the strains (termed non-core genes). We found that DBA/2J uniquely has a substantial majority (89%) of DEGs that are more highly expressed in females than males; 129/SvImJ is the most strongly male-biased with a majority (69%) of DEGs that are more highly expressed in males. To gain insight into the sex-biased DEGs, we examined gene ontology, pathway and phenotype enrichment and found significant enrichment in phenotypes related to abnormal nervous system morphology and physiology, among others. In addition, several pathways are enriched significantly, including Alzheimer’s disease (AD), with 32 genes implicated in AD, 8 of which are male-biased. Three of the male-biased genes have been implicated in a neuroprotective role in AD. Our transcriptomic data provide new insight into understanding the possible genetic bases for sex-specific susceptibility and severity of brain disorders. Overall design: Hippocampal mRNA from adult males and females of six inbred strains of mice were analyzed by RNA sequencing of 3 biological replicates using an Illumina HiSeq 2500
Publication Title
Transcriptomic analysis of the hippocampus from six inbred strains of mice suggests a basis for sex-specific susceptibility and severity of neurological disorders.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Psoriasis is a complex inflammatory disease resulting from the activation of T helper (Th) 1 and Th17 cells. Recent evidence suggests that abnormal activation of Toll-like receptors (TLRs) 7, 8 and 9 contributes to the initiation and maintenance of psoriasis. We have evaluated the effects of TLR antagonists on the gene expression profile in an IL-23-induced skin inflammation model in mice. Psoriasis-like skin lesions were induced in C57BL/6 mice by intradermal injection of IL-23 in the dorsum. Two TLR antagonists were compared: IMO-3100, an antagonist of TLRs 7 and 9, and IMO-8400, an antagonist of TLRs 7, 8 and 9, both of which previously have been shown to reduce epidermal hyperplasia in this model. Skin gene expression profiles of IL-23-induced inflammation were compared with or without TLR antagonist treatment. IL-23 injection resulted in alteration of 5100 gene probes (fold change 2, FDR < 0.05) including IL-17 pathways that are up-regulated in psoriasis vulgaris. Targeting TLRs 7, 8 and 9 with IMO-8400 resulted in modulation of more than 2300 mRNAs while targeting TLRs 7 and 9 with IMO-3100 resulted in modulation of more than 1900 mRNAs. Both agents strongly decreased IL-17A expression (>12-fold reduction), normalized IL-17 induced genes such as beta-defensin and CXCL1, and normalized aberrant expression of keratin 16 (indicating epidermal hyperplasia). These results suggest that IL-23-driven inflammation in mouse skin may be dependent on signaling mediated by TLRs 7, 8, and 9 and that these receptors represent novel therapeutic targets in psoriasis vulgaris and other diseases with similar pathophysiology.
Publication Title
Suppression of molecular inflammatory pathways by Toll-like receptor 7, 8, and 9 antagonists in a model of IL-23-induced skin inflammation.
Sample Metadata Fields
Treatment
View Samples