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GSE65415
Arabidopsis thaliana
6 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
TIR-type nucleotide-binding leucine-rich repeat domain proteins (TNLs) constitute one major group of immune receptors in dicotyledonous plants. Under normal conditions, TNLs can detect non-self or modified-self within the plant cytoplasm to activate immune signaling characterized by extensive transcriptional reprogramming and efficiently counteracting pathogen infection. At the same time, TNLs, in negative epistatic interaction with a second endogeneous locus or allele are causal for induction of autoimmunity or hybrid necrosis. Both native, pathogen-induced TNL responses and autoimmunity are fully dependent on the plant-specific lipase-like protein EDS1, which is a central integrator for all TNL-mediated responses. EDS1 signals within structurally similar, but spatially distinct complexes with PAD4 and SAG101. We here analyzed stable transgenic lines expressing an EDS1 fusion with enforced nuclear localization. Even in absence of SAG101, nuclear-localized EDS1-PAD4 complexes are fully sufficient to function in basal and effector-triggered immunity. Furthermore, we show that nuclear EDS1, when expressed to high levels, can induce autoimmuity in combination with an RPP1-like gene cluster from ecotype Ler. RPP1-like genes are also implicated in several cases of hybrid necrosis, and we can identify the RPP1 paralog R8 as causal for autoimmunity induction by nuclear EDS1 and a previously characterized, EMS-induced mutation. This highlights the important role of EDS1-family proteins in the nuclear compartment in different immune-like responses.
Publication Title
Arabidopsis thaliana DM2h (R8) within the Landsberg RPP1-like Resistance Locus Underlies Three Different Cases of EDS1-Conditioned Autoimmunity.
Sample Metadata Fields
Treatment, Time
View Samples- Homo sapiens
- 10 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
Pancreatic beta-cell dysfunction and death are central in the pathogenesis of type 2 diabetes. Saturated fatty acids cause beta-cell failure and contribute to diabetes development in genetically predisposed individuals. Here we used RNA-sequencing to map transcripts expressed in five palmitate-treated human islet preparations, observing 1,325 modified genes. Palmitate induced fatty acid metabolism and endoplasmic reticulum (ER) stress. Functional studies identified novel mediators of adaptive ER stress signaling. Palmitate modified genes regulating ubiquitin and proteasome function, autophagy and apoptosis. Inhibition of autophagic flux and lysosome function contributed to lipotoxicity. Palmitate inhibited transcription factors controlling beta-cell phenotype including PAX4 and GATA6. 59 type 2 diabetes candidate genes were expressed in human islets, and 11 were modified by palmitate. Palmitate modified expression of 17 splicing factors and shifted alternative splicing of 3,525 transcripts. Ingenuity Pathway Analysis of modified transcripts and genes confirmed that top changed functions related to cell death. DAVID analysis of transcription binding sites in palmitate-modified transcripts revealed a role for PAX4, GATA and the ER stress response regulators XBP1 and ATF6. This human islet transcriptome study identified novel mechanisms of palmitate-induced beta-cell dysfunction and death. The data point to crosstalk between metabolic stress and candidate genes at the beta-cell level. Overall design: 5 human islet of Langerhans preparations examined under 2 conditions (control and palmitate treatment)
Publication Title
RNA sequencing identifies dysregulation of the human pancreatic islet transcriptome by the saturated fatty acid palmitate.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Previous studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild type PR, but with significantly reduced latency (median leukemia-free survival of 274 days versus 473 days for wild type PR, p<0.001). Resistance to proteolysis may increase the abundance of full length PR protein in early myeloid cells, and our previous data suggested that non-cleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.
Publication Title
A protease-resistant PML-RAR{alpha} has increased leukemogenic potential in a murine model of acute promyelocytic leukemia.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 127 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The characteristics of immune cells infiltrating pediatric brain tumors is largely unexplored. A better understanding of these characteristics will provide a foundation for development of immunotherapy for pediatric brain tumors.
Publication Title
Characterization of distinct immunophenotypes across pediatric brain tumor types.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 104 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To better understand the pathogenesis of acute promyelocytic leukemia (APL, FAB M3 AML), we identified genes that are expressed differently in APL cells compared to other acute myeloid leukemia subtypes, and to normal promyelocytes. Comparative gene expression analysis of 14 M3, 62 other AML (M0, M1, M2 and M4) and 5 enriched normal promyelocyte samples revealed a signature of 1,121 genes that are specifically dysregulated in M3 samples relative to other AML, and that do not simply represent normal promyelocyte expression (M3-specific signature). We used a novel, high throughput digital platform (Nanostring's nCounter system) to evaluate a subset of the most significantly dysregulated genes in 30 AML samples; 33 of 37 evaluable gene expression patterns were validated. In an additional analysis, we selected only genes that are dysregulated in M3 both compared to other AML subtypes, and to purified normal CD34+ cells, promyelocytes, and/or neutrophils, thereby isolating a 478 gene "composite M3 dysregulome". Surprisingly, the expression of only a few of these genes was significantly altered in PR-9 cells after PML-RARA induction, suggesting that most of these genes are not direct targets of PML-RARA. Comparison of the M3-specific signature to our previously described murine APL dysregulome revealed 33 commonly dysregulated genes, including JUN, EGR1, and TNF. Collectively, these results suggest that PML-RARA initiates a transcriptional cascade which generates a unique downstream expression signature in both primary human and mouse APL cells.
Publication Title
High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples.
Sample Metadata Fields
Sex, Race
View Samples- Bos taurus
- 88 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Establishment of an in vitro system to explore molecular mechanisms of mastitis susceptibility in cattle by comparative expression profiling of Escherichia coli and Staphylococcus aureus inoculated primary cells sampled from cows with different genetic predisposition for somatic cell score
Publication Title
Comparative expression profiling of E. coli and S. aureus inoculated primary mammary gland cells sampled from cows with different genetic predispositions for somatic cell score.
Sample Metadata Fields
Disease, Treatment, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
sh RNA of p73 in Fibroblasts compared to non-silencing control
Publication Title
p73 poses a barrier to malignant transformation by limiting anchorage-independent growth.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared molecular characteristics of primary and recurrent pediatric ependymoma to identify sub-group specific differences.
Publication Title
Molecular sub-group-specific immunophenotypic changes are associated with outcome in recurrent posterior fossa ependymoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Engineering of genetically encoded calcium indicators predominantly focused on optimizing fluorescence changes, but effects of indicator expression on host organisms have largely not been addressed. Here, we report biocompatibility and wide-spread functional expression of the genetically encoded calcium indicator TN-XXL in a transgenic mouse model. To validate the model and to characterize potential effects of indicator expression we assessed both indicator function and a variety of host parameters such as anatomy, physiology, behavior and gene expression profiles in these mice. We also demonstrate the usefulness of primary cell types and organ explants prepared from these mice for imaging applications. While we do find mild signatures of indicator expression that may guide further indicator development the green indicator mice generated provide a well characterized resource of primary cells and tissues for in vitro and in vivo calcium imaging applications.
Publication Title
Biocompatibility of a genetically encoded calcium indicator in a transgenic mouse model.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 146 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Inflammatory response has been identified as a molecular signature of high-risk Group A ependymoma (EPN). To better understand the biology of this phenotype and aid therapeutic development, transcriptomic data from Group A and B EPN patient tumor samples, and additional malignant and normal brain data, were analyzed to identify the mechanism underlying EPN group A inflammation.
Publication Title
Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples