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GSE56345
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This study revealed pathogenic role of pre-BCR-independent SYK activation in high-risk B-ALL.
Publication Title
Therapeutic potential of spleen tyrosine kinase inhibition for treating high-risk precursor B cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 36 Downloadable Samples
IlluminaHiSeq2500
Description
The transcriptome of zebrafish embryos treated with a Nodal signaling inhibitor at sphere stage, which causes neural tube defects, is compared to those treated at 30% epiboly, which does not. Overall design: Transcriptomic analysis of differential gene expression of key developmental pathways under differing inhibitory treatments.
Publication Title
Identification of transcripts potentially involved in neural tube closure using RNA sequencing.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Protein synthesis belongs to the most energy consuming processes in the cell. Lowering oxygen tension below normal (hypoxia) causes a rapid inhibition of global mRNA translation due to the decreased availability of energy. Interestingly, subsets of mRNAs pursue active translation under such circumstances. In human fibrosarcoma cells (HT1080) exposed to prolonged hypoxia (36 h, 1% oxygen) we observed that transcripts are either increasingly or decreasingly associated with ribosomes localized at the endoplasmic reticulum (ER). In a global setting it turned out that only 31% of transcripts showing elevated total-RNA levels were also increasingly present at the ER in hypoxia. These genes, regulated by its expression as well as its ER-localization, belong to the gene ontologys hypoxia response, glycolysis and HIF-1 transcription factor network supporting the view of active mRNA translation at the ER during hypoxia. Interestingly, a large group of RNAs was found to be unchanged at the expression level, but translocate to the ER in hypoxia. Among these are transcripts encoding translation factors and >180 ncRNAs. In summary, we provide evidence that protein synthesis is favoured at the ER and, thus, partitioning of the transcriptome between cytoplasmic and ER associated ribosomes mediates adaptation of gene expression in hypoxia.
Publication Title
Hypoxia-induced gene expression results from selective mRNA partitioning to the endoplasmic reticulum.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
We used microarray analysis to investigate if keratinocytes excert an immuno-inflammatory response towards streptococcal M1 protein.
Publication Title
Vigilant keratinocytes trigger pathogen-associated molecular pattern signaling in response to streptococcal M1 protein.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Social experience influences multiple behaviors of many animal species, including aggression. Social isolation often increases aggressiveness. To investigater the molecular basis of social influences on aggressiveness, we performed comparative gene expression profiling on heads from 6-day-old, single-housed, more aggressive and group-housed, less aggressive male flies.
Publication Title
A common genetic target for environmental and heritable influences on aggressiveness in Drosophila.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina HiSeq 2000
Description
The Wnt gene family is an evolutionarily conserved group of proteins that regulate cell growth, differentiation, and stem cell self-renewal. Aberrant Wnt signaling in human breast tumors has been proposed to be an attractive drug target, especially in the basal-like subtype where canonical Wnt signaling is both enriched and predictive of poor clinical outcomes. The development of effective Wnt based therapeutics, however, has been slowed in part by a limited understanding of the context dependent nature with which these aberrations influence breast tumorigenesis. We recently reported that MMTV-Wnt1 mice, which are an established model for studying Wnt signaling in breast tumors, develop two subtypes of tumors by gene expression classification: Wnt1-EarlyEx and Wnt1-LateEx. Here, we extend this initial observation and show that Wnt1-EarlyEx tumors had high expression of canonical Wnt, non-canonical Wnt, and EGFR signaling pathway signatures. Therapeutically, Wnt1-EarlyEx tumors had a dynamic reduction in tumor volume when treated with an EGFR inhibitor. Wnt1-EarlyEx tumors also had primarily Cd49fpos/Epcamneg FACS profiles, but were unable to be serially transplanted into wild-type FVB female mice. Wnt1-LateEx tumors, conversely, had a bloody gross pathology, which was highlighted by the presence of 'blood lakes' by H&E staining. These tumors had primarily Cd49fpos/Epcampos FACS profiles, but also contained a secondary Cd49fpos/Epcamneg subpopulation. Wnt1-LateEx tumors were enriched for activating Hras1 mutations and were capable of reproducing tumors when serially transplanted into wild-type FVB female mice. This study definitely shows that the MMTV-Wnt1 mouse model produces two phenotypically distinct subtypes of mammary tumors. Importantly, these subtypes differ in their therapeutic response to an EGFR inhibitor, suggesting that a subset of human tumors with aberrant Wnt signaling may also respond to erlotinib. Overall design: Agilent gene expression microarrays were performed comparing RNA from FVB/n MMTV-Wnt1 mammary tumors to a common mouse reference sample. Agilent CGH microarrays were performed comparing DNA from FVB/n MMTV-Wnt1 mammary tumors to DNA from FVB wild-type mice. RNAseq libraries were prepared from FVB/n MMTV-Wnt1 mammary tumors using a TruSeq RNA kit before being submitted to the Lineberger Comprehensive Cancer Center Genomics Core to be run on the Illumina HiSeq 2000.
Publication Title
The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We used the flu mutant of Arabidopsis and a transgenic line that overexpresses the thylakoid-bound ascorbate peroxidase (tAPX) to address the interactions between different reactive oxygen species (ROS) signaling pathways. The conditional flu mutant of Arabidopsis accumulates excess protochlorophyllide in the dark within chloroplast membranes that upon illumination acts as a photosensitizer and generates singlet oxygen (1O2). Immediately after the release of singlet oxygen rapid changes in nuclear gene expression occur. Distinct sets of genes were activated that were different from those induced by other reactive oxygen species, superoxide or hydrogen peroxide (H2O2), suggesting that different types of active oxygen species activate distinct signaling pathways. It was not known whether the pathways operate separately or interact with each other. We have addressed this problem by modulating noninvasively the level of H2O2 in plastids by means of a transgenic line that overexpresses the thylakoid-bound ascorbate peroxidase (tAPX, line 14/2 PMID: 15165186). In the flu mutant overexpressing tAPX, the expression of most of the nuclear genes that were rapidly activated after the release of 1O2 was significantly higher in flu plants overexpressing tAPX, whereas in wild-type plants, overexpression of tAPX had only a very minor impact on nuclear gene expression. The results suggest that H2O2 antagonizes the 1O2-mediated signaling of stress responses as seen in the flu mutant. This cross-talk between H2O2- and 1O2-dependent signaling pathways might contribute to the overall stability and robustness of wild-type plants exposed to adverse environmental stress conditions.
Publication Title
Cross-talk between singlet oxygen- and hydrogen peroxide-dependent signaling of stress responses in Arabidopsis thaliana.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 56 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53 null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in nave hosts.
Publication Title
Murine microenvironment metaprofiles associate with human cancer etiology and intrinsic subtypes.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 29 Downloadable Samples
- Illumina HiSeq 2500
Description
Climate change and disease have large negative impacts on poultry production, but little is known about the interactions of responses to these stressors in chickens. Fayoumi (heat and disease resistant) and broiler (heat and disease susceptible) chicken lines were stimulated at 22 days of age, using a 2x2x2 factorial design including: breed (Fayoumi or broiler), inflammatory stimulus [lipopolysaccharide (LPS) or saline], and temperature (35°C or 25°C). Transcriptional changes in spleens were analyzed using RNA-sequencing on the Illumina HiSeq 2500. Thirty-two individual cDNA libraries were sequenced (four per treatment) and an average of 22 million reads were generated per library. Stimulation with LPS induced more differentially expressed genes (DEG, log2 fold change = 2 and FDR = 0.05) in the broiler (N=283) than the Fayoumi (N=85), whereas heat treatment resulted in fewer DEG in broiler (N=22) compared to Fayoumi (N=107). The double stimulus of LPS+heat induced the largest numbers of changes in gene expression, for which broiler had 567 DEG and Fayoumi had 1471 DEG of which 399 were shared between breeds. Further analysis of DEG revealed pathways impacted by these stressors such as Remodelling of Epithelial Adherens Junctions due to heat stress, Granulocyte Adhesion and Diapedesis due to LPS, and Hepatic Fibrosis/Hepatic Stellate Cell Activation due to LPS+heat. The genes and pathways identified provide deeper understanding of the response to the applied stressors and may serve as biomarkers for genetic selection for heat and disease tolerant chickens. Overall design: At 22 days of age, divergent chicken breeds (Fayoumi and broiler) were treated with a thermal treatment (heat stress at 35C, or thermoneutral at 25C as a control) for 3.5 hours, then stimulated subcutaneously with an inflammatory stimulus (LPS, or saline as a control) for another 3.5 hours. Chickens were euthanized and spleens were harvested. A total of 32 indivudally coded cDNA libraries were prepared using TruSeq v2 library preparation kit which selects for polyA mRNA. In this 2x2x2 full factorial design with the factors of breed, thermal treatment, and inflammatory stimulus, there were a total of 8 treatment groups. Each treatment group had a total of 4 animal biological replicates. Therefore, a total of 32 individual barcoded samples were sequenced. A total of 8 individually barcoded cDNA libraries were sequenced per lane using the HiSeq Illumina 2500, and we used 4 lanes total. Reads were mapped to Galgal 2.0.
Publication Title
Unique genetic responses revealed in RNA-seq of the spleen of chickens stimulated with lipopolysaccharide and short-term heat.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sle1c is a sublocus of the NZM2410-derived Sle1 major susceptibility locus. We have previously shown that Sle1c contributes to lupus pathogenesis by conferring CD4+ T cell-intrinsic hyperactivation and increased susceptibility to chronic graft-versus-host disease (cGVHD) that mapped to the centromeric portion of the locus. In this study, we have refined the centromeric sublocus to a 675Kb interval, termed Sle1c2. Recombinant congenic strains expressing Sle1c2 exhibited a T cell-intrinsic CD4+ T cell hyperactivation and cGVHD susceptibility, similar to mice with the parental Sle1c.
Publication Title
Murine lupus susceptibility locus Sle1c2 mediates CD4+ T cell activation and maps to estrogen-related receptor γ.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples