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SRP059217
Homo sapiens
16 Downloadable Samples
IlluminaHiSeq2500
Description
Smooth muscle cell (SMC) phenotypic switching from a contractile to a synthetic state is implicated in diverse vascular pathologies, including neointimal formation. This study was designed to identify lncRNAs that may play a role in vascular pathologies. Primary smooth muscle cells cultured from surplus human saphenous vein tissue were treated with inflammatory and proliferative stimuli, IL1a and PDGF, for 72h and RNA extracted for RNA-sequencing. Using edgeR processed data we found expression of many lncRNAs was altered following treatment and could play a role in vascular disease. Overall design: 4 groups of samples, n= 3/group each replicate using cells cultured from a different venous patient sample. Cells were quiesced in 0.2% serum for 48h followed by addition of 10ng/ml IL1a , 20ng/ml PDGF or both 10ng/ml IL1a and 20ng/ml PDGF together. Cells were collected after 72h and RNA extracted using Qiagen RNeasy kits. RNA-sequencing was carried out by Beckman Coulter Genomics on the r-RNA depleted fraction.
Publication Title
Smooth Muscle Enriched Long Noncoding RNA (SMILR) Regulates Cell Proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
The synthesis and processing of mRNA, from transcription to translation initiation, often requires splicing of intragenic material. The final mRNA composition varies based upon proteins that modulate splice site selection. EWS-FLI1 is an Ewing sarcoma (ES) oncogene with an interactome that we demonstrate to have multiple partners in spliceosomal complexes. We evaluate EWS-FLI1 upon post-transcriptional gene regulation using both exon array and RNA-seq. Genes that potentially regulate oncogenesis including CLK1, CASP3, PPFIBP1, and TERT validate as alternatively spliced by EWS-FLI1. EWS-FLI1 also alters splicing by directly binding to known splicing factors including DDX5, hnRNPK, and PRPF6. Reduction of EWS-FLI1 produces an isoform of g-TERT that has increased telomerase activity compared to WT TERT. The small molecule YK-4-279 is an inhibitor of EWS-FLI1 oncogenic function that disrupts specific protein interactions including DDX5 and RNA helicase A (RHA) that alters RNA splicing ratios. As such, YK-4-279 validates the splicing mechanism of EWS-FLI1 showing alternatively spliced gene patterns that significantly overlap with EWS-FLI1 reduction and WT human mesenchymal stem cells. Exon array analysis of 75 ES patient samples show similar isoform expression patterns to cell line models expressing EWS-FLI1, supporting the clinical relevance of our findings. These experiments establish systemic alternative splicing as an oncogenic process modulated by EWS-FLI1. EWS-FLI1 modulation of mRNA splicing may provide insight into the contribution of splicing towards oncogenesis, and reciprocally, EWS-FLI1 interactions with splicing proteins may inform the splicing code.
Publication Title
Oncogenic fusion protein EWS-FLI1 is a network hub that regulates alternative splicing.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Here we report the discovery of highly potent and selective EZH2 small molecule inhibitors, their validation by a cellular thermal shift assay, their application across a large lymphoma cell panel and their efficacy in GCBDLBCL xenograft models. Overall design: RNA-seq of KARPAS-422 cell line RNA, in duplicate, treated with DMSO as control, and EZH2 inhibitors CPI360, EPZ-6438 and GSK126. Eight samples in total.
Publication Title
EZH2 inhibitor efficacy in non-Hodgkin's lymphoma does not require suppression of H3K27 monomethylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Differential gene expression in RNA isolated from stably-transfected EBERs-negative versus EBERs-positive HK1 cell lines
Publication Title
Deregulation of lipid metabolism pathway genes in nasopharyngeal carcinoma cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systems biology of interstitial lung diseases: integration of mRNA and microRNA expression changes.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 29 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis.
Publication Title
Systems biology of interstitial lung diseases: integration of mRNA and microRNA expression changes.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microvesicles (MV) are small membrane-bound particles comprised of exosomes and various sized extracellular vesicles. These are released by a number of cell types. Microvesicles have a variety of cellular functions from communication to mediating growth and differentiation. Microvesicles contain proteins and nucleic acids. Previously, we showed that plasma microvesicles contain microRNAs (miRNAs). Based on our previous report, the majority of peripheral blood microvesicles are derived from platelets while mononuclear phagocytes, including macrophages, are the second most abundant population. Here, we characterized macrophage-derived microvesicles and whether they influenced the differentiation of nave monocytes. We also identified the miRNA content of the macrophage-derived microvesicles. We found that RNA molecules contained in the macrophage-derived microvesicles were transported to target cells, including monocytes, endothelial cells, epithelial cells and fibroblasts. Furthermore, we found that miR-223 was transported to target cells and was functionally active. Based on our observations, we hypothesize that microvesicles bind to and activate target cells. Furthermore, we find that microvesicles induce the differentiation of macrophages. Thus, defining key components of this response may identify novel targets to regulate host defense and inflammation.
Publication Title
Macrophage microvesicles induce macrophage differentiation and miR-223 transfer.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Chromosomal translocation t(8;21) (q22;q22) leading to generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is a cytogenetic abnormality observed in about 10% of acute myelogenous leukemia (AML). To uncover somatic mutations that cooperate with t(8;21)-driven leukemia, we performed targeted and whole exome sequencing of newly-diagnosed and relapsed AML samples. We identified high frequency of truncating alterations in ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and DHX15 in this subtype of AML. To investigate in-depth the role of ASXL2 in normal and malignant hematopoiesis, we utilized a mouse model of ASXL2 deficiency. Loss of ASXL2 caused progressive hematopoietic defects characterized by myeloid cell expansion, splenomegaly, extramedullary hematopoiesis and poor reconstitution ability in transplantation models. A parallel analysis of young and >1-year old Asxl2-deficient mice revealed age-dependent changes in the hematopoietic compartment leading to perturbations affecting not only myeloid and erythroid differentiation but also maturation of lymphoid cells. Our studies also suggest that expression of truncated ASXL2 protein confers proliferative advantage to mouse myeloid progenitors. Overall, these findings establish a critical role of ASXL2 in maintaining steady state hematopoiesis and provide insights into how its loss/mutation primes leukemic growth of myeloid cells. Overall design: Bone marrow derived LSK cells from young (8-12 weeks old) and >1-year old Asxl2 WT and knockout mice were analyzed for gene expression changes.
Publication Title
ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid expansion.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Genome-wide gene expression changes in response to CBP inhibitor treatment in Treg cells using RNA sequencing (RNA-seq). Overall design: Expression profiling by RNA-seq of Treg cells treated with DMSO or CBP inhibitor
Publication Title
Regulatory T Cell Modulation by CBP/EP300 Bromodomain Inhibition.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Genome-wide gene expression changes in response to CBP inhibitor treatment in Treg cells using microarray.
Publication Title
Regulatory T Cell Modulation by CBP/EP300 Bromodomain Inhibition.
Sample Metadata Fields
Cell line, Treatment
View Samples