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GSE27914
Homo sapiens
31 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The proto-oncogenes ETV1, ETV4, and ETV5 encode members of the E26 transformation-specific (ETS) transcription factor family, which includes the most frequently rearranged and overexpressed genes in prostate cancer. Despite being critical regulators of development, little is known about their post-translational regulation. Here we identify the ubiquitin ligase COnstitutive Photomorphogenic-1 (COP1, also called RFWD2) as a tumor suppressor that negatively regulates ETV1, ETV4, and ETV5. ETV1, which is the member mutated more frequently in prostate cancer, was degraded after being ubiquitinated by COP1. Truncated ETV1 encoded by prostate cancer translocation TMPRSS2:ETV1 lacks the critical COP1 binding motifs (degrons) and was 50-fold more stable than wild-type ETV1. Almost all patient translocations eliminate these ETV1 degrons, implying that translocations rendering ETV1 insensitive to COP1 confer a significant selective advantage to prostate epithelial cells. Indeed, COP1 deficiency in mouse prostate elevated ETV1 levels and produced increased cell proliferation, hyperplasia, and early prostate intraepithelial neoplasia. The combined loss of COP1 and PTEN enhanced the invasiveness of mouse prostate adenocarcinomas. Finally, relatively rare human prostate cancer samples showed hemizygous loss of the COP1 gene, loss of COP1 protein expression, and abnormally elevated ETV1 protein while lacking a translocation event. These findings identify COP1 as a bona fide tumor suppressor whose down-regulation promotes prostatic epithelial cell proliferation and tumorigenesis.
Publication Title
COP1 is a tumour suppressor that causes degradation of ETS transcription factors.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Abstract. The role of platelets in hemostasis and thrombosis is clearly established; however, the mechanisms by which platelets mediate inflammatory and immune pathways are less well understood. Platelets interact and modulate the function of blood and vascular cells by releasing bioactive molecules. Although the platelet is anucleate, it contains transcripts that may mirror disease. Platelet mRNA is only associated with low-level protein translation, however, platelets have a unique membrane structure allowing for the passage of small molecules, leading to the possibility that its cytoplasmic RNA may be passed to nucleated cells. To examine this question, platelet-like particles with labeled RNA were co-cultured with vascular cells. Co-culture of platelet-like particles with activated THP-1, monocytic, and endothelial cells led to visual and functional RNA transfer. Post-transfer microarray gene expression analysis of THP-1 cells showed an increase in HBG1/HBG2 and HBA1/HBA2 expression which was directly related to the transfer. Infusion of wild-type platelets into a TLR2 deficient mouse model established in vivo confirmation of select platelet RNA transfer to leukocytes. By specifically transferring green fluorescent protein, it was also observed that external RNA was functional in the recipient cells. The observation that platelets possess the capacity to transfer cytosolic RNA suggests a new function for platelets in the regulation of vascular homeostasis.
Publication Title
Platelets and platelet-like particles mediate intercellular RNA transfer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The objectives of this study were to understand the effect of phenolic compounds from fermented berry beverages on hyperglycemia and obesity in vivo using mice fed a high fat diet. Our hypothesis was that consumption of a fermented blueberry-blackberry beverage and its phenolic compounds would reduce the development of obesity and hyperglycemia in diet-induced obese mice. Body composition, histomorphological analysis of pancreatic islets and liver, and expression of genes involved in obesity and hyperglycemia were evaluated in order to explain the modulation of diet-induced obesity and hyperglycemia due to treatments.
Publication Title
Alcohol-free fermented blueberry-blackberry beverage phenolic extract attenuates diet-induced obesity and blood glucose in C57BL/6J mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina Genome Analyzer
Description
This report not only adds a novel mechanism to the current dogma on achieving global shortening of 3''UTRs, but also unveils a novel function of the NMD pathway in establishing tissue-specific transcriptome identity Overall design: We first generated prospermatogonia-specific Upf2 conditional knockout mice (Ddx4-Cre; Upf2 fl/?, hereafter called Ddx4-KO) by crossing Ddx4-Cre13 with Upf2 floxed.
Publication Title
UPF2-Dependent Nonsense-Mediated mRNA Decay Pathway Is Essential for Spermatogenesis by Selectively Eliminating Longer 3'UTR Transcripts.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2000
Description
Cap Analysis of Gene Expression (CAGE) applied on carbon nanotubes exposed lung tissue to identify alternative promoter and enhancer usage after 24 hr of exposure in order to investigate the nature of the response observed in these mice. Overall design: C57BL/6 mice was exposed to vehicle or multi walled carbon nanotubes (MWCNT) by intratracheal installation. 5 mice was exposed to 162 ug of MWCNTs ( XNRI-7; lot05072001K28, Hadoga Chemical industry (formerly known as Mitsui) disolved in 0.9% NaCl and 10% v/v cellfree cellular broncho alveolar lavage (BAL) fluid collected from C57BL/6 mice. 6 mice was exposed to the previously decribed saline/BAL solution but without carbon nanotubes.
Publication Title
Identification of Gene Transcription Start Sites and Enhancers Responding to Pulmonary Carbon Nanotube Exposure in Vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 119 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CONTEXT Slowly progressive chronic tubulo-interstitial damage jeopardizes long-term renal allograft survival. Both immune and non-immune mechanisms are thought to contribute, but the most promising targets for timely intervention have not been identified. OBJECTIVE In the current study we seek to determine the driving force behind progressive histological damage of renal allografts, without the interference of donor pathology, delayed graft function and acute graft rejection. DESIGN We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. PATIENTS Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection. RESULTS In this highly cross-validated study, we demonstrate the significant association of established, ongoing and future chronic histological damage with regulation of adaptive immune gene expression (T-cell and B-cell transcript sets) and innate immune response gene expression (dendritic cell, NK-cell, mast cell and granulocyte transcripts). We demonstrate the ability of gene expression analysis to perform as a quantitative marker for ongoing inflammation with a wide dynamic range: from subtle subhistological inflammation prior to development of chronic damage, over moderate subclinical inflammation associated with chronic histological damage, to marked inflammation of Banff-grade acute T-cell mediated rejection. CONCLUSION Progressive chronic histological damage after kidney transplantation is associated with significant regulation of both innate and adaptive immune responses, months before the histological lesions appear. This study therefore corroborates the hypothesis that quantitative inflammation below the diagnostic threshold of classic T-cell or antibody-mediated rejection is associated with early subclinical stages of progressive renal allograft damage.
Publication Title
Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Spleen and lymph node dendritic cells have a differential capacity do induce and retain iTreg cells. Therefore we performed a comparative analysis of the dendritic cells derived from these two compartments to identify the responsible genes
Publication Title
Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 63 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Plasma cells (PCs) as effectors of humoral immunity produce immunoglobulins to match pathogenic insult. However, emerging data suggests more diverse roles for PCs as regulators of immune and inflammatory responses via secretion of factors other than immunoglobulins. The extent to which such responses are pre-programmed in B-lineage cells or can be induced in PCs by the microenvironment is unknown. Here we dissect the impact of IFNs on the regulatory networks of human plasma cells. We show that core PC programs are unaffected, while PCs respond to IFNs with distinctive transcriptional responses. The ISG15-system emerges as a major transcriptional output induced in a sustained fashion by IFN- in PCs and linked both to intracellular conjugation and ISG15 secretion. This leads to the identification of ISG15-secreting plasmablasts/PCs in patients with active SLE. Thus ISG15-secreting PCs represent a distinct pro-inflammatory PC subset providing an immunoglobulin-independent mechanism of PC action in human autoimmunity
Publication Title
Network Analysis Identifies Proinflammatory Plasma Cell Polarization for Secretion of ISG15 in Human Autoimmunity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Background: Increasing evidence indicates stem cell transplantation may be an effective stroke treatment but little is known about the direct impact of transplanted cells on injured brain tissue. We investigated the effects of lineage negative murine hematopoietic stem/progenitor cells (HSPCs) on the cerebral microcirculation following ischemia-reperfusion injury (I/RI). Following subsequent evaluation of the mRNA transcriptome of the explanted HSPCs, we assessed whether metallothionein (MT)-1, (increased in explanted HSPCs from I/R mice) administration was able to evoke similar neuro-protection following cerebral I/RI. Methods and Results: Murine HSPCs administered intravenously 24 hours (h) post cerebral I/R were selectively recruited to the brain of I/RI mice. Mice treated with HSPCs displayed decreased disease severity for up to 2-weeks post cerebral I/R, as evidenced by decreased mortality rate, decreased infarct volume, improved functional outcome, reduced microglial activation and elevated plasma levels of anti-inflammatory interleukin-10. Using confocal intravital microscopy, we found that transplanted cells had emigrated into the brain parenchyma and that RNA-seq analysis of explanted HSPCs indicated significantly increased levels of metallothionein transcripts, in particular MT-1. We further determined that treatment of mice with MT-1 significantly reduced neurological score and IV. Conclusions: These studies provide further evidence for HSPCs as a promising therapeutic strategy in promoting repair following cerebral I/RI, potentially via a MT-1 mechanism. Overall design: Murine HSPCs were administered into mice with I/RI intravenously 24 hours post cerebral I/R and selectively recruited to the brain. RNA profiles of explanted HSPCs were determined by RNA sequencing.
Publication Title
Metallothionein I as a direct link between therapeutic hematopoietic stem/progenitor cells and cerebral protection in stroke.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 47 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: circular RNAs are a class of endogenous RNAs with various functions in eukaryotic cells. Worthy of note, circular RNAs play a critical role in cancer. Currently, nothing is known about the role of circular RNAs in head and neck squamous cell carcinoma (HNSCC). The identification of circular RNAs in HNSCC might become useful for diagnostic and therapeutic strategies in HNSCC.
Publication Title
The oncogenic role of circPVT1 in head and neck squamous cell carcinoma is mediated through the mutant p53/YAP/TEAD transcription-competent complex.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples