Filters
Technology
Platform
SRP144520
Homo sapiens
6 Downloadable Samples
Illumina HiSeq 2000
Description
Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in Acute Myeloid Leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that “non-mutated” splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This led to the identification of the splicing regulator RBM25 as a novel tumor suppressor, and down-regulation of RBM25 increased proliferation and decreased apoptosis in human leukemic cell lines. Mechanistically, we could show that RBM25 controlled the splicing of key genes, including those encoding the apoptotic regulator BCL-x and the MYC inhibitor BIN1. Specifically, we demonstrated that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels. This mechanism also appears to be operative in human AML patients where RBM25 levels correlative inversely with MYC activity and clinical outcome. Overall design: Examined transcriptome from U937 cells in biological triplicates.
Publication Title
The splicing factor RBM25 controls MYC activity in acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 10 Downloadable Samples
Arabidopsis Gene 1.0 ST Array (aragene10st)
Description
We wanted to understand at what level BTS acts, i.e. how upstream BTS acts and if BTS misregulation affets only a subset or multiple subsets of Fe regulated genes. We studied WT and bts-3 mutant roots.
Publication Title
BRUTUS and its paralogs, BTS LIKE1 and BTS LIKE2, encode important negative regulators of the iron deficiency response in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Plexiform neurofibroma is a major contributor to morbidity in Neurofibromatosis type I (NF1) patients. Macrophages and mast cells infiltrate neurofibroma, and data from mouse models implicate these leukocytes in neurofibroma development. Anti-inflammatory therapy targeting these cell populations has been suggested as a means to prevent neurofibroma development. Here, we compare gene expression in inflamed nerves from NF1 models which invariably form neurofibroma to those with inflammation driven by EGFR overexpression which rarely progresses to neurofibroma. We find that the chemokine Cxcl10 is uniquely up-regulated in NF1 mice that invariably develop neurofibroma. Global deletion of the CXCL10 receptor, Cxcr3, prevented neurofibroma development in these neurofibroma-prone mice. Cxcr3 expression localized to T cells and dendritic cells (DCs) in both inflamed nerves and neurofibromas. These data support a heretofore unappreciated role for T cells/DCs in neurofibroma initiation. Overall design: To identify cell populations associated with Cxcl10 expression, we utilized a single-cell RNA-Seq (scRNA-Seq) data set collected from 2-month Dhh-Cre;Nf1 fl/fl nerve/DRG using the 10x Genomics Chromium platform.
Publication Title
Cxcr3-expressing leukocytes are necessary for neurofibroma formation in mice.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Infection of Kaposi's sarcoma associated herpes virus (KSHV) has been linked to the development of primary effusion lymphoma (PEL), which is characterized by the loss of expression of B cell markers and effusions in the body cavities. This unique clinical feature of PEL has been attributed to their distinctive gene expression profile which shows overexpression of genes in various signaling pathways. KSHV-encoded latent protein vFLIP K13 has been shown to promote the survival and proliferation of PEL cells. In this study, we have employed gene array analysis followed by bioinformatics analysis of coordinated transcriptional factors network as well as biological pathways to characterize the effect of K13 on PEL-derived BCBL1 cells. We observed that genes associated with Cytokine signaling, Cell death, NF-kappaB and Cell adhesion pathways were differentially regulated by K13.
Publication Title
A computational profiling of changes in gene expression and transcription factors induced by vFLIP K13 in primary effusion lymphoma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Integrated microarray and multiplex cytokine analyses of Kaposi's Sarcoma Asssociated Herpesvirus viral FLICE Inhibitory Protein K13 affected genes and cytokines in human blood vascular endothelial cells. The KSHV-encoded K13 protein is one of the few proteins to be expressed in latently-infected spindle cells and the ectopic expression of K13 in human vascular endothelial cells is sufficient to transform them into spindle cells.
Publication Title
Integrated microarray and multiplex cytokine analyses of Kaposi's Sarcoma Associated Herpesvirus viral FLICE Inhibitory Protein K13 affected genes and cytokines in human blood vascular endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We report here that KSHV viral infection targets the NF-kB pathway which is crucial for cell survival. KSHV protein vFLIP K13 is known to directly interact with cellular protein NEMO of the NF-kB pathway. We used gene expression array to suggets that the interaction of K13 with NEMO is important to activate NF-kB pathway.
Publication Title
NEMO is essential for Kaposi's sarcoma-associated herpesvirus-encoded vFLIP K13-induced gene expression and protection against death receptor-induced cell death, and its N-terminal 251 residues are sufficient for this process.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Linker histone H1 is a protein component of chromatin and has been linked to chromatin compaction and global gene silencing.It has been sugegsted that H1 plays a significant role, regulating a relatively small number of genes. Here we show that H1.2- a variant of H1 subtype is recruited to chromatin region and is dependent on EZH2-mediated H3K27me3. Therefore a Gene expression array analysis was carried out with H1.2 as well as EZH2 knockout MCF7 cells to confirm the interlationship of H1.2 and EZH2 activity.
Publication Title
Linker histone H1.2 establishes chromatin compaction and gene silencing through recognition of H3K27me3.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
PURPOSE: The goal of this study was to determine the gene expression networks regulated by tumor necrosis factor receptor 2 (TNFR2, or Tnfrsf1b) and to evaluate their potential bearing on immune cell subsets and inflammatory bowel disease (IBD). METHODS: mRNA-seq was performed on isolated distal colons from TNFR2-knockout and wildtype mice. Differentially expressed transcripts were compared to human ulcerative colitis microarray datasets on Gene Expression Omnibus and to mouse immunological expression datasets at the Immunological Genome Project. RESULTS: We identified 252 mouse transcripts whose expressions were significantly altered by the loss of TNFR2. The majority of these transcripts (228 of 252, ~90%) were downregulated in TNFR2-/- colons. TNFR2-regulated genes were able to positively discriminate between ulcerative colitis patients and healthy individuals with ~80% accuracy. Many TNFR2-regulated genes were also highly expressed in CD8+ T cells. CONCLUSIONS: Downregulation of TNFR2 is associated with a gene expression profile that is prominent in IBD and supportive of the role of CD8+ T cells in IBD pathogenesis. MANUSCRIPT ABSTRACT: Increased tumor necrosis factor (TNF) production has been associated with inflammatory bowel disease (IBD), and anti-TNF therapy is a common therapeutic for this patient population. However, the role of TNF or its receptors (TNFR1 and TNFR2) in the immunopathogenesis of inflammatory bowel disease (IBD) remains unclear. Here we report that TNFR2 is protective in spontaneous (IL-10 knockout) and chemically (azoxymethane/dextran sodium sulfate)-induced mouse models of colitis and colitis-associated cancer. Mechanistically, TNFR2-deficiency in hematopoietic cells significantly increased incidence and severity of colitis and colitis-associated cancer characterized by a selective expansion of CD8+ T cells. We identified TNFR2-regulated genes in the colon that were specific for CD8+ T cells, interacted with multiple IBD risk genes, and are important regulators of CD8+ T cell biology. TNFR2 regulated CD8+ T-cell-specific genes that act as genetic susceptibility modifiers for IBD to mitigate the development of a pro-colitogenic milieu. Antibody-mediated depletion of CD8+ T cells prevented colonic inflammation and significantly reduced pathology in IL10-/-/TNFR2-/- deficient mice. Furthermore, adoptive transfer of TNFR2-/- naïve CD8+ T cells resulted in more severe disease than with wildtype naïve CD8+ T cells. Our findings provide insight into the disease modifier role of TNFR2 in the immunopathogenesis of IBD through the modulation of CD8+ T cell responses and support future investigation of this therapeutic target, especially in the subset of IBD patients with CD8+ T-cell dysfunction. Overall design: Total RNA from distal colons of 8 week-old male wildtype C57Bl/6 and TNFR2-/- mice (n=3 each) was isolated using the PureLink RNA kit (Ambion, Life Technologies). RNA samples were submitted to the Genomic Services Lab at the HudsonAlpha Institute for Biotechnology (Huntsville, AL) for multiplex library preparation, mRNA enrichment, and sequencing. Sequencing was performed to an average depth of 50M paired-end 50bp reads per sample (HiSeq, Illumina, San Diego, CA). Data files containing raw reads were aligned to the mouse genome using Tophat2/Bowtie2. Alignments were assembled into transcript representations with Cufflinks, and statistical tests for differential expression were performed with Cuffdiff 2. An adjusted P value < 0.05 (q<0.05) from the Cuffdiff 2 output was used as the cutoff for statistical significance.
Publication Title
Tumor Necrosis Factor Receptor 2 Restricts the Pathogenicity of CD8(+) T Cells in Mice With Colitis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- NextSeq 500
Description
Mesenchymal stem cells (MSCs) are multipotent progenitor cells present in various mesenchymal tissues that undergo strict lineage-specific differentiation programs, faithful to their unique tissue origins. However, the key regulators that activate dental pulp MSC commitment to odontogenesis remain unclear. In this study, we utilized an inducible Cre/loxP system to interrupt BMP signaling in apical MSCs at the onset of molar root formation in order to investigate the functional requirement for BMP signaling and its downstream targets in MSC cell fate determination during tooth morphogenesis. Overall design: mRNA profiling of MSC to study role of BMP signaling in tooth morphogenesis
Publication Title
BMP signaling orchestrates a transcriptional network to control the fate of mesenchymal stem cells in mice.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Though limited proteolysis of the histone H3 N-terminal tail (H3NT) is frequently observed during mammalian differentiation, however the specific genomic sites targeted for H3NT proteolysis and their functional significance of H3NT cleavage remain unknown.We used genome wide RNA-seq approaches to an established cell model of osteoclast differentiation. We discovered that H3NT proteolysis is selectively targeted near transcription start sites of a small group of genes and that most of these H3NT-cleaved genes are epigenetically regulated during osteoclastogenesis.We have identified that the principal H3NT protease of osteoclastogenesis is matrix metalloproteinase 9 (MMP-9). We next studied genomewide mRNA expression in MMP9 knockout cells and its effect in the epigenetic reprogramming of gene pathways required for proficient osteoclastogenesis. Overall design: Differential expresssion profile of transcripts in wt and MMP9 knockout cells
Publication Title
MMP-9 facilitates selective proteolysis of the histone H3 tail at genes necessary for proficient osteoclastogenesis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples