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Danio rerio
1 Downloadable Sample
IlluminaHiSeq2500
Description
The goal of the experiment was to determine the transcriptional expression profile of zebrafish thrombocytes in order to enable comparison with mouse and human platelets. Overall design: Thrombocyte isolation from Tg(cd41:EGFP) zebrafish peripheral blood was performed using a novel monoclonal antibody (3H9) to Cd41
Publication Title
Sorting zebrafish thrombocyte lineage cells with a Cd41 monoclonal antibody enriches hematopoietic stem cell activity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cytoplasmic DNA triggers the activation of the innate immune system. While downstream signaling components have been characterized, the DNA sensing components remain largely elusive. We performed a systematic proteomics screen for proteins that associate with DNA, traversed to a screen for IFN--induced transcripts. We identified DSIRE (DNA sensor for the IL-1 response, previously called AIM2) as a candidate cytoplasmic sensor. DSIRE showed a marked selectivity for double-stranded DNA. DSIRE can recruit the inflammasome adaptor ASC and gets redistributed to ASC speckles upon coexpression of ASC. RNAi-mediated reduction of DSIRE expression led to an impairment in IL-1 maturation. Reconstitution of unresponsive cells with DSIRE, ASC, caspase 1 and IL-1 showed that DSIRE is sufficient for inflammasome activation. Overall, our data strongly suggest that DSIRE is a cytoplasmic DNA sensor for the inflammasome.
Publication Title
An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Purpose: We identified KPC1 as the ubiquitin ligase that binds to the p105 precursor of NF-kB, ubiquitinates it and mediates its proteasomal processing to generate the p50 active subunit of the transcription factor. Using U87-MG human glioblastoma xenografts, we observed that overexpression of KPC1 results in strong inhibition of tumor growth mediated via excessive generation of p50.The goal of this RNASeq study was to analyze the profile of gene expression in xenografts overexpressing control (V0), KPC1 or p50 vectors, and to further understand how the altered gene expression patterns can explain the tumor suppressive effect we observed. Results:Transcript analysis of U87-MG xenografts overexpressing control (V0), KPC1 or p50 vector mapped to the human genome revealed: • A strong similarity between overexpression of p50 and KPC1 (correlation of 0.51, p-value<10-300 ) • A specific signature of NF-kB targets [21 of the consistently changed genes are known to be regulated by NF-kB (p-value<3.4×10-9 )] • A significant (p-value<1.4×10-18) increase in the expression of 40 tumor suppressor genes, with no significant change in other classes. • A significant down regulation of a cluster of genes including LIN28B, IL-6, HMAGA2 and VEGFA. This finding links well to an established regulatory axis involving LIN28B, Let-7 microRNA, and IL-6 in inflammation and cell transformation that is regulated by NF-kB. Overall design: Exponentially growing U87-MG cells were stably transfected with an empty vector (V0) or vectors coding for Myc-KPC1 or Flag-p50. Cells were dissociated with trypsin, washed with PBS, and brought to a concentration of 50×10^6 cells/ml. Cell suspension (5×10^6/0.1 ml) was inoculated subcutaneously at the right flank of 7-weeks old male Balb/C nude mice (n=7). Following 21 days, mRNA from U87-MG xenografts was isolated using an RNA purification kit, and analyzed using the Illumina HiSeq 2500 sequencer. The RNASeq analysis experiment was repeated twice independently. Run1 included a total of 7 samples. Samples 1-3 were isolated from V0 – control tumors (3 different tumors), samples 4-5 were isolated from KPC1-expressing tumors (2 different pools of 3 tumors each due to small tumor size), and samples 6-7 were isolated from p50-expressing tumors for (2 different pools of 2-3 tumors each, due to very small tumor size). Run2 included a total of 5 samples. Samples 8-10 were isolated from V0 (control) tumors (3 different tumors), samples 11-12 were isolated from KPC1 tumors (2 different pools of 3 tumors each due to small tumor size). Several repeated attempts to extract RNA from the p50-expressing tumors did not yield any results, as the tumors were miniscule.
Publication Title
KPC1-mediated ubiquitination and proteasomal processing of NF-κB1 p105 to p50 restricts tumor growth.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Breast cancer is genetically heterogeneous, and recent studies have underlined a prominent contribution of epigenetics to the development of this disease. To uncover new synthetic lethalities with known breast cancer oncogenes, we screened an epigenome-focused short hairpin RNA library on a panel of engineered breast epithelial cell lines. Here we report a selective interaction between the NOTCH1 signaling pathway and the SUMOylation cascade. Knockdown of the E2-conjugating enzyme UBC9 (UBE2I) as well as inhibition of the E1-activating complex SAE1/UBA2 using ginkgolic acid impairs the growth of NOTCH1-activated breast epithelial cells. We show that upon inhibition of SUMOylation NOTCH1-activated cells proceed slower through the cell cycle and ultimately enter apoptosis. Mechanistically, activation of NOTCH1 signaling depletes the pool of unconjugated small ubiquitin-like modifier 1 (SUMO1) and SUMO2/3 leading to increased sensitivity to perturbation of the SUMOylation cascade. Depletion of unconjugated SUMO correlates with sensitivity to inhibition of SUMOylation also in patient-derived breast cancer cell lines with constitutive NOTCH pathway activation. Our investigation suggests that SUMOylation cascade inhibitors should be further explored as targeted treatment for NOTCH-driven breast cancer. Overall design: We treated MCF10A and NOTCH1 cells with either DMSO or ginkgolic acid 30 uM for 3 days. Two replicates have been analysed for each condition.
Publication Title
NOTCH1 activation in breast cancer confers sensitivity to inhibition of SUMOylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Hepatitis C virus (HCV) infection is a global health problem. A number of studies have implicated a direct role of cellular lipid metabolism in the HCV life cycle and inhibitors of the mevalonate pathway have been demonstrated to result in an antiviral state within the host cell. Transcriptome profiling was also conducted on Huh-7 human hepatoma cells bearing subgenomic HCV replicons with and without treatment with 25-hydroxycholesterol (25-HC), an inhibitor of the mevalonate pathway that alters lipid metabolism, to assess metabolic determinants of pro- and antiviral states within the host cell.
Publication Title
Transcriptional profiling of the effects of 25-hydroxycholesterol on human hepatocyte metabolism and the antiviral state it conveys against the hepatitis C virus.
Sample Metadata Fields
No sample metadata fields
View Samples
SRP096656- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
SW480 cells were treated with 2uM crizotinib for 72h (versus DMSO) Overall design: Examination of differential up- or down-regulated genes after crizotinib treatment
Publication Title
Global survey of the immunomodulatory potential of common drugs.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 28 Downloadable Samples
- Illumina HiSeq 2500
Description
At the cellular level, a-tubulin acetylation alters the structure of microtubules to render them mechanically resistant to compressive forces. How this biochemical property of microtubule acetylation relates to mechanosensation remains unknown, though prior studies have shown that microtubule acetylation influences touch perception. Here, we identify the major Drosophila a-tubulin acetylase (dTAT) and show that it plays key roles in several forms of mechanosensation. dTAT is highly expressed in the larval peripheral nervous system (PNS), but is largely dispensable for neuronal morphogenesis. Mutation of the acetylase gene or the K40 acetylation site in a-tubulin impairs mechanical sensitivity in sensory neurons and behavioral responses to gentle touch, harsh touch, gravity, and vibration stimuli, but not noxious thermal stimulus. Finally, we show that dTAT is required for mechanically-induced activation of NOMPC, a microtubule-associated transient receptor potential channel, and functions to maintain integrity of the microtubule cytoskeleton in response to mechanical stimulation. Overall design: Six neuronal and non-neuronal cell types of Drosophila melanogaster larvae, with 100 cells each and at least four biological replicates were profiled by mRNA-Seq
Publication Title
Microtubule Acetylation Is Required for Mechanosensation in Drosophila.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2000
Description
A basal (MDAMB468) and luminal (ZR75-1) cell line were treated with DMSO or PKC412 for 6h Overall design: 2 DMSO and 3 PKC412 treated samples for each cell line
Publication Title
Targeting a cell state common to triple-negative breast cancers.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Huh7/5-2 cells (Binder et al., Hepatology 2007) were mock infected (DMEM) (time points 4 and 48 h) or infected with the chimeric HCV virus Jc1 (Pietschmann et al., PNAS 2006) (all time points).
Publication Title
Viral immune modulators perturb the human molecular network by common and unique strategies.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In order to explore molecules whose expression is controlled by Slc39a13, we investigated gene expression profiling of primary chondrocyte isolated from wild-type and Slc39a13 knockout mice.
Publication Title
The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways.
Sample Metadata Fields
No sample metadata fields
View Samples