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SRP169631
Mus musculus
10 Downloadable Samples
NextSeq 500
Description
ROR?t is well recognized as the lineage defining transcription factor for TH17 cell development. However, the cell-intrinsic mechanisms that negatively regulate TH17 cell development and autoimmunity remain poorly understood. Here we demonstrate that the transcriptional repressor REV-ERBa is exclusively expressed in TH17 cells, competes with ROR?t for their shared DNA consensus sequence, and negatively regulates TH17 cell development via repression of genes traditionally characterized as ROR?t-dependent, including Il17a. Deletion of REV-ERBa enhanced TH17-mediated pro-inflammatory cytokine expression, exacerbating experimental autoimmune encephalomyelitis (EAE) and colitis. Treatment with REV-ERB-specific synthetic ligands, which have similar phenotypic properties as ROR? modulators, suppressed TH17 cell development, was effective in colitis intervention studies, and significantly decreased the onset, severity, and relapse rate in several models of EAE without affecting thymic cellularity. Our results establish that REV-ERBa negatively regulates pro-inflammatory TH17 responses in vivo and identifies the REV-ERBs as potential targets for the treatment of TH17-mediated autoimmune diseases. Overall design: 10 samples; 5 conditions with 2 replicates per condition
Publication Title
REV-ERBĪ± Regulates T<sub>H</sub>17 Cell Development and Autoimmunity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sickle cell disease is characterized by hemolysis, vaso-occlusion and ischemia reperfusion injury. These events cause endothelial dysfunction and vasculopathies in multiple systems
Publication Title
Global gene expression profiling of endothelium exposed to heme reveals an organ-specific induction of cytoprotective enzymes in sickle cell disease.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To compare up-regulation of genes following CpG activation, we performed microarray analysis of activated macrophages from B6 and F1(B6xMOLF) mouse strains. Cells were activated for 0, 2 and 4 hrs with 200nM of type B CpG. Levels of mRNA for many genes differened dramatically between the strains
Publication Title
Mannose receptor 1 mediates cellular uptake and endosomal delivery of CpG-motif containing oligodeoxynucleotides.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Plasmablastic lymphoma is a high grade B cell lymphoma with plasmablastic morphology and a terminally differentiated B cell immunophenotype, usually arising in the setting of immunodeficiency and often demonstrating Epstein Barr Virus positivity. The molecular and genetic mechanisms underlying the pathogenesis of PBL are largely unknown. To better understand its pathogenesis, herein we have analyzed global gene expression of PBL and compared that to gene expression profiles of diffuse large B cell lymphoma. While overlaps in transcriptomes between these malignancies were identified, we have shown that the gene expression profile of plasmablastic lymphoma is distinct, demonstrating striking downregulation of B cell receptor signaling genes, BCL6, BCL11A SPI-B, targets of NFKB1, and upregulation of mitochondrial genes, PRMT5, MYC and MYC targets and IL21, implicating these alterations in the pathogenesis of this lymphoma. In addition we show the usefulness of SWAP-70 immunohistochemistry in the differentiation of immunoblastic diffuse large B cell lymphoma and plasmablastic lymphoma. Our findings provide justification for considering plasmablastic lymphoma as a specific lymphoma entity and provide insight into the unique transcriptional aberrations occurring in this high-grade lymphoma.
Publication Title
Gene expression analysis of plasmablastic lymphoma identifies downregulation of B-cell receptor signaling and additional unique transcriptional programs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The tumor microenvironment plays a critical role in cancer progression, but the precise mechanisms by which stromal cells influence the tumor epithelium are poorly understood. The signaling adapter p62 has been implicated as a positive regulator of epithelial tumorigenesis; however, its role in the stroma is unknown. We show here that p62 levels are reduced in the stroma of several tumors. Also, orthotopic and organotypic studies demonstrate that the loss of p62 in the tumor microenvironment or stromal fibroblasts resulted in increased tumorigenesis of epithelial prostate cancer cells. The mechanism involves the regulation of cellular redox through an mTORC1/c-Myc pathway of stromal glucose and amino acid metabolism. Inhibition of the pathway by p62 deficiency results in increased stromal IL-6 production, which is required for tumor promotion in the epithelial compartment. Thus, p62 is an anti-inflammatory tumor suppressor that acts through modulation of metabolism in the tumor stroma.
Publication Title
Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
mRNA and microRNA expression was examined in global cellular fractions and in RNA-induced silencing complex (RISC)-immunoprecipitated cell fractions in cultured primary human astrocytes (ScienCell) and in cultured human U-87 MG astrocytoma cells (ATCC). ABSTRACT: Background: GW/P bodies are cytoplasmic ribonucleoprotein-rich foci that are involved in microRNA (miRNA)-mediated messenger RNA (mRNA) silencing and degradation. These mRNA regulatory functions within GW/P bodies are mediated by GW182 and its binding partner hAgo2 when bound to miRNA within the RNA-induced silencing complex (RISC). Although miRNAs and mRNAs are known to be localized to RISC in a variety of cells, to date no published study has examined the profile of specific miRNA and mRNA targeted to the RISC. Methodology/Principle Findings: In this study, RISC mRNA and miRNA components were profiled by microarray analysis of human U-87 astrocytoma cells and primary human astrocytes with total RNA extracted from the RISC as well as the global cellular fractions. The novel findings of this study were fourfold: (1) miRNAs are highly enriched in primary astrocyte RISC compared to U-87 astrocytoma RISC, (2) astrocytoma cells and primary astrocytes each contain unique RISC miRNA profiles as compared to their respective cellular miRNA profiles, (3) miR-195, 10b, 29b, 19b, 34a and 455-3p were upregulated and miR-181b was downregulated in U-87 astrocytoma RISC as compared to primary astrocyte RISC, and (4) RISC contain mostly downregulated mRNAs in primary astrocytes and U-87 astrocytoma cells. Conclusions/Significance: We show that in U-87 astrocytoma cells, miR-34a and miR-195 were upregulated in RISC suggesting an oncogenic role for these miRNAs. Three miR34a-targeted mRNAs and two miR-195-targeted mRNAs were downregulated. One miR-195-targeted mRNA was upregulated. Biological pathway analysis of RISC mRNA components suggests that the RISC plays a pivotal role in cancer, inflammatory disease, immunological disease, the cell cycle, cellular movement and numerous cell signaling pathways. This study points to the importance of the RISC and ultimately GW/P body composition and function and in miRNA and mRNA deregulation in astrocytoma cells and possibly for other brain tumors.
Publication Title
The microRNA and messengerRNA profile of the RNA-induced silencing complex in human primary astrocyte and astrocytoma cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina Genome Analyzer II
Description
We generated knock-in mice expressing GFP under the control of the endogenous GIP (Glucose-dependent Insulinotropic Polypeptide) promoter that enable the isolation of a purified population of small intestine K cells. Using RNA-Seq, we comprehensively characterized the transcriptomes of GIP-GFP cells as well as the entire enteroendocrine lineage derived from Neurogenin3 (Ngn3)-expressing progenitors. Overall design: We interrogated the whole transcriptome of FACS-isolated small intestine GIPGFP cells using high-throughput mRNA sequencing. We also obtained the global gene expression patterns of the entire enteroendocrine cell lineage as well as the non-enteroendocrine cell population, comprising enterocytes, goblet cells and Paneth cells. To achieve this, small intestine epithelial cells from male mice resulting from the breeding of Neurogenin3 (Ngn3)-Cre mice with ROSA26-LoxP-STOP-LoxP-tomato indicator mice were isolated based on Tomato fluorescence and negative staining for CD45. Due to the small cell numbers, we constructed each of the three RNA-Seq libraries (GIPGFP, Ngn3TOMATO, and Ngn3-) using a pool of equal amounts of individual RNA samples without RNA amplification.
Publication Title
RNA-Seq analysis of enteroendocrine cells reveals a role for FABP5 in the control of GIP secretion.
Sample Metadata Fields
No sample metadata fields
View Samples- Hordeum vulgare
- 144 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
A split-split-plot design with 144 experimental units (3 replications x 4 genotypes x 6 time points x 2 treatment types) was used to profile barley plants containing variants of Mla1 and Mla6 powdery mildew resistance genes in response to inoculation with the Blumeria graminis f. sp. hordei (Bgh) isolates 5874 (AvrMla1, AvrMla6). Barley leaves were harvested from inoculated and non-inoculated plants at 6 time points (0,8,16,20,24 and 32 hrs) after Bgh inoculation. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Rico Caldo. The equivalent experiment is BB10 at PLEXdb.]
Publication Title
Blufensin1 negatively impacts basal defense in response to barley powdery mildew.
Sample Metadata Fields
Specimen part, Time
View Samples- Hordeum vulgare
- 60 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
Barley stripe mosaic virus-induced gene silencing (BSMV-VIGS) was used to identify significant new genes in the regulation of host innate immunity. This experiment was designed to uncover significant changes in Bln1 (Contig12219_at)-silenced plants relative to empty vector and buffer treated controls. Five independent biological replications of a split-plot experimental design were conducted with replications as blocks, treatment with Blumeria graminis f. sp. hordei (Bgh) as the whole-plot factor, and all combinations of genotype (Mla13 and Mla9) and VIGS treatment [Buffer control (mock), BSMV:00 (empty vector), and BSMV:Bln1248] as the split-plot factor for a total of 60 GeneChip hybridizations. Ten seedlings were used as a split-plot experimental unit for each combination of replication, Bgh treatment, genotype, and VIGS treatment. Plants were grown in a controlled 20C glasshouse prior to VIGS treatment. Twelve days after VIGS treatment, half of the plants in each replication were challenged with the compatible Bgh isolate 5874. Top halves of 5 of the 10 seedling third leaves (about 10 cm) from each split-plot experimental unit were harvested into liquid N2 at 32 hours after inoculation (HAI) - the timepoint with the highest differential Bln1 transcript accumulation (Meng et al. 2009), and after initial establishment of the perihaustorial interface (Caldo et al. 2004). The remaining 5 leaves were used to record infection phenotype 7 days later. RNA was isolated for GeneChip hybridization from the 32-HAI samples. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Yan Meng. The equivalent experiment is BB101 at PLEXdb.]
Publication Title
Blufensin1 negatively impacts basal defense in response to barley powdery mildew.
Sample Metadata Fields
Age, Specimen part
View Samples- Hordeum vulgare
- 32 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
A parallel expression profiling of wild-type and loss-of-function mutants of Mla6 and Mla1 powdery mildew resistance alleles was conducted using Barley1 GeneChip. Barley plants were inoculated with powdery mildew isolate 5874 and first leaves were harvested at 6 time points after pathogen inoculation. This experiment was conducted in split-split-plot experimental design with 3 replications.
Publication Title
Blufensin1 negatively impacts basal defense in response to barley powdery mildew.
Sample Metadata Fields
Age, Specimen part, Time
View Samples