Inhibition of miR-33 results in increased cholesterol efflux and HDL-cholesterol levels in mice. In this study we examined the effect of miR-33 inhibition in a mouse model of atherosclerosis and observed significant reduction in atherosclerotic plaque size. At the end of the study, gene expression in macrophages from the atherosclerotic plaques was assessed.
Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis.
Sex, Specimen part
View SamplesThe expression profiles of 64 neuroblastic tumors (mainly neuroblastoma) were determined on Affymetrix chips HG U133 Plus 2.0.
Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma.
No sample metadata fields
View SamplesOrganophosphorus compounds may induce neurotoxicity through mechanisms other than the cholinergic pathway, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis.
Toxicogenomic studies of human neural cells following exposure to organophosphorus chemical warfare nerve agent VX.
Specimen part
View SamplesPlasmodium falciparum malaria severely impacts human health. In order to broaden our understanding of merozoite invasion of erythrocytes which is responsible for clinical disease, a P. falciparum -irradiated "long-lived merozoite" (LLM) line was investigated. Cell-sieve purified LLM invaded human erythrocytes with an improved efficiency of 10- to 300-fold greater than wild-type (WT) parasites. A comparison of their genomes identified limited changes in the open reading frame of LLM; while only marginal differences were observed in the transcriptomes. Analysis of their proteomes by quantitative mass-spectrometry identified 446 out of 981 proteins of known or unknown function with a significant change in protein abundance (ANOVA p < 0.05). Furthermore, the relative molar concentration of nearly 1100 merozoite proteins was established. Unfortunately, a specific change being responsible for the LLM phenotype was not identified. However, immunoblot analyses of LLM lysates showed proteolytic processing of some proteins of the MSP1 complex and AMA1 were delayed, suggesting that this delayed proteolysis positively impacted merozoite viability and subsequent invasion.
Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach.
No sample metadata fields
View SamplesTranscriptome analysis by RNAseq of leukemia model promoted by MLL-Af4 or MLL-AF9 fusion proteins. We find each fusion protein promotes a specific gene signature correlating to those identified in patients Overall design: Human CD34+ hematopoietic stem and progenitor cells were transduced with retrovirus expressing MLL-Af4 or MLL-AF9. Transduced cells were transplanted into immunodeficient mice to induce lymphoid leukemia or placed in myeloid in vitro culture. CD19+ lymphoid leukemia cells (3 AF9, 6 Af4), control health CD19+CD34+ proB cells (n=3) and 4 pairs of Af4 and AF9 CD33+CD19- myeloid culture cells were collected for RNA-seq
Instructive Role of MLL-Fusion Proteins Revealed by a Model of t(4;11) Pro-B Acute Lymphoblastic Leukemia.
No sample metadata fields
View Samples15-25% of breast cancers (BC) show ERBB2-amplification and overexpression of the encoded ERBB2 tyrosine kinase receptor. They are associated with a poor prognosis but can benefit from targeted therapy. A better knowledge of these BCs may help understand their behavior and design new therapeutic strategies. In this study, we defined the high resolution genome and gene expression profiles of 54 ERBB2-amplified BCs using 244K oligonucleotide array-comparative genomic hybridization and whole-genome DNA microarrays. We first identified the ERBB2-C17orf37-GRB7 genomic segment as the minimal common amplicon, and CRKRS and IKZF3 as the most frequent centromeric and telomeric amplicon borders, respectively. Second, we identified 17 genome regions affected by copy number aberration (CNA). The expression of 37 genes of these regions was deregulated. Third, two types of heterogeneity were observed in ERBB2-amplified BCs. The genomic profiles of estrogen receptor-postive (ER+) and negative (ER-) ERBB2-amplified BCs were different. The WNT/-catenin signaling pathway was involved in ER- ERBB2-amplified BCs, and PVT1 and TRPS1 were candidate oncogenes associated with ER+ ERBB2-amplified BCs. The size of the ERBB2-amplicon was different in inflammatory (IBC) and non inflammatory BCs. ERBB2-amplified IBCs were characterized by the downregulated and upregulated mRNA expression of ten and two genes in proportion to CNA, respectively. We have shown that ERBB2 BCs are heterogeneous and identified genomic features that may be useful in the design of therapeutical strategies
Genome profiling of ERBB2-amplified breast cancers.
No sample metadata fields
View SamplesLung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor “activated/reprogrammed” stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM)-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils) identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value. Overall design: We sorted pure populations of the immature monocytic myeloid cells (IMMCs), neutrophils (Neu), and epithelial cells (Epi) from tumors and adjacent lung tissues of stage I-III lung adenocarcinoma patients. RNA samples (totally 17 samples) were sequenced: from tumor IMMC (n=3), Neu (n=2), Epi (n=2); from adjacent lung IMMC (n=3), Neu (n=4), Epi (n=3).
Identification of Reprogrammed Myeloid Cell Transcriptomes in NSCLC.
No sample metadata fields
View SamplesIschemic cardiopathy is the leading cause of death in the world, for which efficient regenerative therapy is not currently available. In mammals, after a myocardial infarction episode, the damaged myocardium is replaced by scar tissue featuring collagen deposition and tissue remodelling with negligible cardiomyocyte proliferation. Zebrafish, in contrast, display an extensive regenerative capacity as they are able to restore completely lost cardiac tissue after partial ventricular amputation. Due to the lack of genetic lineage tracing evidence, it is not yet clear if new cardiomyocytes arise from existing contractile cells or from an uncharacterised set of progenitors cells. Nonetheless, several genes and molecules have been shown to participate in this process, some of them being cardiomyocyte mitogens in vitro. Though questions as what are the early signals that drive the regenerative response and what is the relative role of each cardiac cell in this process still need to be answered, the zebrafish is emerging as a very valuable tool to understand heart regeneration and devise strategies that may be of potential value to treat human cardiac disease. Here, we performed a genome-wide transcriptome profile analysis focusing on the early time points of zebrafish heart regeneration and compared our results with those of previously published data. Our analyses confirmed the differential expression of several transcripts, and identified additional genes the expression of which is differentially regulated during zebrafish heart regeneration. We validated the microarray data by conventional and/or quantitative RT-PCR. For a subset of these genes, their expression pattern was analyzed by in situ hybridization and shown to be upregulated in the regenerating area of the heart. The specific role of these new transcripts during zebrafish heart regeneration was further investigated ex vivo using primary cultures of zebrafish cardiomyocytes and/or epicardial cells. Our results offer new insights into the biology of heart regeneration in the zebrafish and, together with future experiments in mammals, may be of potential interest for clinical applications.
Transcriptomics approach to investigate zebrafish heart regeneration.
Specimen part, Time
View SamplesTo get insight in the functional role of EGR2 for Ewing sarcoma, we performed a transcriptional profiling of Ewing sarcoma cells after knockdown of EGR2 and compared the resulting transcriptional signature with that of EWSR1-FLI1-silenced Ewing sarcoma cells. In accordance with the strong EGR2-induction by EWSR1-FLI1, both genes highly significantly overlap in their transcriptional signatures. Gene-set enrichment analyses (GSEA) and DAVID (Database for Annotation, Visualisation and Integrated Discovery) gene ontology analyses indicated a strong impact of EGR2 on cholesterol and lipid biosynthesis resembling its function in orchestrating lipid metabolism of myelinating Schwann cells.
Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite.
Cell line, Treatment
View SamplesNonsense-mediated mRNA decay (NMD) surveillance pathways are best known to be involved in the degradation of mRNA with premature termination codons (PTCs). More recent studies demonstrate that the role of NMD pathways goes well beyond the degradation of PTC containing mRNA, into the regulation of cell function and thus normal development.
Transcriptome profiling of UPF3B/NMD-deficient lymphoblastoid cells from patients with various forms of intellectual disability.
Specimen part, Disease, Disease stage, Cell line, Subject
View Samples