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GSE7275
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Exosomes are vesicles of endocytic origin released by many types of cells into the extracellular environment. In an attempt to further examine the exosome-mediated cellular communication, we show that exosomes from a mouse mast cell line (MC/9), exosomes from primary bone marrow derived mast cells, and exosomes from a human mast cell line (HMC-1) contain RNA but not DNA.
Publication Title
Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Exosomes are nanovesicles of endocytic origin believed to be involved in communication between cells. Recently, it has been shown that mast cell exosomes contain RNA named "exosomal shuttle RNA". The aim of this study was to evaluate whether exosomal shuttle RNA could play a role in the communication between human mast cells and between human mast cells and human CD34 positive progenitor cells. Results: Exosomes from the human mast cell line HMC-1 contain RNA. The exosomes contain no or very little ribosomal RNA compared to their donor cells. The mRNA and microRNA content in exosomes and their donor cells was examined using microarray analyses. We found 116 microRNA in the exosomes and 134 microRNA in the cells, from which some were expressed at different level. DNA microarray experiments revealed the presence of approximately 1800 mRNAs in the exosomes, which represent 15% of the donor cell mRNA content. Transfer experiments revealed that exosomes and their RNA can transfer to other HMC-1 cells and to CD34 positive progenitors. Conclusions: To conclude, HMC-1 exosomes contain mRNA and microRNA that can be transferred to other mast cells and to CD34 progenitors. This shuttle of exosomal RNA may represent a powerful mode of communication between cells where cells send genetic information to other cells over a distance via exosomes.
Publication Title
Characterization of mRNA and microRNA in human mast cell-derived exosomes and their transfer to other mast cells and blood CD34 progenitor cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
CD8+ T cells are pre-programmed for cytotoxic differentiation. However, a subset of effector CD8+ T cells (Tc17) produce IL-17 and fail to express cytotoxic genes. Here, we show that the transcription factors directing IL-17 production inhibit cytotoxicity despite persistent Runx3 expression. Cytotoxic gene repression did not require the transcription factor Thpok. We further show that STAT3 restrained cytotoxic gene expression in CD8+ T cells and that RORgt represses cytotoxic genes by inhibiting the functions but not the expression of the cytotoxic transcription factors T-bet and Eomesodermin. Thus, the transcriptional circuitry directing IL-17 expression inhibits cytotoxic functions.
Publication Title
A STAT3-dependent transcriptional circuitry inhibits cytotoxic gene expression in T cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
CD8+ T cells are pre-programmed for cytotoxic differentiation. However, a subset of effector CD8+ T cells (Tc17) produce IL-17 and fail to express cytotoxic genes. Here, we show that the transcription factors directing IL-17 production inhibit cytotoxicity despite persistent Runx3 expression. Cytotoxic gene repression did not require the transcription factor Thpok. We further show that STAT3 restrained cytotoxic gene expression in CD8+ T cells and that RORgt represses cytotoxic genes by inhibiting the functions but not the expression of the cytotoxic transcription factors T-bet and Eomesodermin. Thus, the transcriptional circuitry directing IL-17 expression inhibits cytotoxic functions.
Publication Title
A STAT3-dependent transcriptional circuitry inhibits cytotoxic gene expression in T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 228 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs are non-coding RNAs involved in the maturation of other RNA molecules. Alterations of sno/scaRNA expression may play a role in cancerogenesis. This study elucidates the patterns of sno/scaRNA expression in highly purified cells from 211 chronic lymphocytic leukemia (CLL) patients (Binet stage A) also in comparison with those of different normal B-cell subsets. CLLs display a sno/scaRNAs expression profile similar to normal memory, nave and marginal-zone B-cells, with the exception of a few down-regulated transcripts (SNORA31, -6, -62, and -71C). Our analyses also suggest some heterogeneity in the pattern of sno/scaRNAs expression which is apparently unrelated to the major biological (ZAP-70 and CD38), molecular (IGHV mutation) and cytogenetic markers. Moreover, we found that SNORA70F was significantly down-regulated in poor prognostic subgroups and this phenomenon was associated with the down-regulation of its host gene COBLL1. Finally, we generated an independent model based on SNORA74A and SNORD116-18 expression, which appears to distinguish two different prognostic CLL groups. These data extend the view of sno/scaRNAs deregulation in cancer and may contribute to discover novel biomarkers associated with the disease and potentially useful to predict the clinical outcome of early stage CLL patients.
Publication Title
Small nucleolar RNAs as new biomarkers in chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
ISWI is an evolutionary conserved ATPase that catalyzes nucleosome remodeling in several different complexes. Two mammalian ISWI orthologs, SNF2H and SNF2L, have specialized functions despite their high similarity. Due to the lack of reagents the functions of SN2L in human cells had not been established. Newly established specific monoclonal antibodies and selective RNA interference protocols now enabled a comprehensive characterization of loss-of-function phenotypes in human cells. Contrasting earlier results obtained in the mouse model, we found SNF2L broadly expressed in primary human tissues. Depletion of SNF2L in HeLa cells led to enhanced proliferation, morphological alterations and increased migration. These phenomena were explained by transcriptome profiling, which identified SNF2L as a modulator of the Wnt signaling network. The cumulative effects of SNF2L depletion on gene expression portray the cell in a state of activated Wnt signaling characterized by increased proliferation and chemotactic locomotion. High levels of SNF2L expression in normal melanocytes contrast to undetectable expression in malignant melanoma. In summary, our data document an anti-correlation between SNF2L expression and several features characteristic of malignant cells.
Publication Title
Nucleosome remodeler SNF2L suppresses cell proliferation and migration and attenuates Wnt signaling.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MicroRNAs (miRs) function primarily as post-transcriptional negative regulators of gene expression through binding to their mRNA targets. Reliable prediction of a miRs targets is a considerable bioinformatic challenge of great importance for inferring the miRs function. Sequence-based prediction algorithms have high false-positive rates, are not in agreement, and are not biological context specific. Here we introduce CoSMic (Context-Specific MicroRNA analysis), an algorithm that combines sequence-based prediction with miR and mRNA expression data. CoSMic differs from existing methodsit identifies miRs that play active roles in the specific biological system of interest and predicts with less false positives their functional targets. We applied CoSMic to search for miRs that regulate the migratory response of human mammary cells to epidermal growth factor (EGF) stimulation. Several such miRs, whose putative targets were significantly enriched by migration processes were identified. We tested three of these miRs experimentally, and showed that they indeed affected the migratory phenotype; we also tested three negative controls. In comparison to other algorithms CoSMic indeed filters out false positives and allows improved identification of context-specific targets. CoSMic can greatly facilitate miR research in general and, in particular, advance our understanding of individual miRs function in a specific context.
Publication Title
Context-specific microRNA analysis: identification of functional microRNAs and their mRNA targets.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 188 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 188 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Highly homologous B-cell receptors, stereotyped BCR, are expressed in a recurrent fraction of patients with chronic lymphocytic leukemia (CLL). In this study, we investigated the biological and molecular features of leukemic cells from 16 patients utilizing stereotyped subset #4 BCR (IGHV4-34) in a prospective cohort of 462 Binet stage A CLL patients. All subset #4 patients were characterized by the IGHV mutated gene configuration and by the absence of unfavorable cytogenetic lesions, and NOTCH1 and SF3B1 mutations. Gene expression profiling demonstrated a significant downregulation of WDFY4, MF2A and upregulation of PDGFA, FGFR1 and TFEC genes in leukemic cells from subset #4 compared to those from the remaining IGHV-mutated patients. Similarly, in the cells from subset #4 cases there was a specific miRNA expression pattern involving the upregulation of miR-497 and miR-29c. Furthermore transfection of miR-497 mimic in primary leukemic CLL cells induced a downregulation of BCL2, known to be a validated target of this miRNA. Our data identify a distinct gene and miRNA expression profile of the cells from subset #4 patients, providing further evidence for the putative role of BCR in shaping the features of the leukemic cells.
Publication Title
Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
IlluminaHiSeq2000
Description
p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-?B subunit. Moreover, it partly shifts p53’s conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator. Overall design: MCF10A cells transfected with siRNA against LATS1/2 alone, p53 alone or LATS1/2 and p53 together. Two independent MCF10A batches provided biological replicates
Publication Title
Down-regulation of LATS kinases alters p53 to promote cell migration.
Sample Metadata Fields
No sample metadata fields
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