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GSE66890
Homo sapiens
59 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Clinical study of critically ill patients with sepsis and sepsis-related ARDS with whole blood RNA collected within the first 24 hours of admission
Publication Title
Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.
Sample Metadata Fields
Sex, Disease, Disease stage
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A chromosomal translocation fusion gene product EWS-WT1 is the defining genetic event in Desmoplastic Small Round Cell Tumor (DSRCT), a rare but aggressive tumor with a high rate of mortality. EWS-WT1 oncogene acts as an aberrant transcription factor that drives tumorigenesis, but the mechanism by which EWS-WT1 causes tumorigenesis is not well understood. To delineate the oncogenic mechanisms, we generated the EWS-WT1 fusion in the mouse using a gene targeting (knock-in) approach, enabling physiologic expression of EWS-WT1 under the native Ews promoter. We derived mouse embryonic fibroblasts (MEFs) and performed genome-wide expression profiling to identify transcripts directly regulated by EWS-WT1. Remarkably, expression of EWS-WT1 led to a dramatic induction of many neuronal genes. Notably, a neural reprogramming factor, ASCL1 (achaete-scute complex-like 1), was highly induced by EWS-WT1 in MEFs and in primary DSRCT. Further analysis demonstrated that EWS-WT1 directly binds to the proximal promoter region of ASCL1 and activates its transcription through multiple WT1-responsive elements. Depletion of EWS-WT1 in a DSRCT cell line resulted in severe reduction in ASCL1 expression and cell viability. Remarkably, when stimulated with neuronal induction media, cells expressing EWS-WT1 expressed neural markers and generated neurite-like projections. These results demonstrate for the first time that EWS-WT1 activates neural gene expression and is capable of directing partial neuronal differentiation, likely via ASCL1. These findings suggest that stimulating DSRCT tumor cells with biological or chemical agents that promote neural differentiation might be a useful approach to develop novel therapeutics against this incurable disease.
Publication Title
EWS-WT1 oncoprotein activates neuronal reprogramming factor ASCL1 and promotes neural differentiation.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Complete polarization of macrophages towards an M1-like proinflammatory and antimicrobial state requires combined action of IFN-? and LPS. Synergistic activation of canonical inflammatory NF-?B target genes by IFN-? and LPS is well appreciated, but less is known about whether IFN-? negatively regulates components of the LPS response, and how this affects polarization. A combined transcriptomic and epigenomic approach revealed that IFN-? selectively abrogates LPS-induced feedback and select metabolic pathways by suppressing TLR4-mediated activation of gene enhancers. In contrast to superinduction of inflammatory genes via enhancers that harbor IRF sequences and bind STAT1, IFN-?-mediated repression targeted enhancers with STAT sequences that bound STAT3. TLR4-activated IFN-?-suppressed enhancers comprised two subsets distinguished by differential regulation of histone acetylation and recruitment of STAT3, CDK8 and cohesin, and were functionally inactivated by IFN-?. These findings reveal that IFN-? suppresses feedback inhibitory and metabolic components of the TLR response to achieve full M1 polarization, and provide insights into mechanisms by which IFN-? selectively inhibits TLR4-induced transcription. Overall design: RNA-seq analysis of transcriptional changes in human macrophages that were cultured with or without IFN-? and then stimulated with LPS
Publication Title
IFN-γ selectively suppresses a subset of TLR4-activated genes and enhancers to potentiate macrophage activation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 57 Downloadable Samples
- NextSeq 500
Description
Intrahepatic cholangiocarcioma has two molecular classification of intrahepatic CCA with distinct clinical, pathological, biological and prognostic differences Overall design: Examination of 2 different cluster of intrahepatic cholangiocarcinoma based on RNA sequencing by NGS
Publication Title
Prognostic subclass of intrahepatic cholangiocarcinoma by integrative molecular-clinical analysis and potential targeted approach.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Macrophages from RA synovial fluids were compared to primary human monocyte-derived macrophages.
Publication Title
Interferon-γ Represses M2 Gene Expression in Human Macrophages by Disassembling Enhancers Bound by the Transcription Factor MAF.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Pro-inflammatory response of VSMCs is triggered by endothelial damage and a causative step for thrombosis and neointimal thickening in the arterial vessels. Therefore, we investigate a role of cytosolic Hsp60 as a novel pro-inflammatory mediator in VSMCs. Hsp60 was detected in the cytosol of VSMCs. The selective depletion of cytosolic Hsp60 in VSMCs reduced the IKK activation, repressed the induction of NF-?B-dependent pro-survival genes (MnSOD and Bfl-1/A1), and enhanced apoptotic death in response to TNF-a. Moreover, a quantitative RNA sequencing revealed that the expression of 75 genes among the 774 TNF-a-inducible genes was significantly reduced by the depletion of cytosolic Hsp60. In particular, the expression of pro-inflammatory cytokines/chemokines, such as CCL2, CCL20, and IL-6, was regulated by the cytosolic Hsp60 in VSMCs. Finally, the depletion of cytosolic Hsp60 markedly inhibited the neointimal thickening in the balloon-injured arterial vessels by inducing apoptotic cell death and inhibiting chemokine production. This study provides the first evidence that cytosolic Hsp60 could be a therapeutic target for preventing inflammation-driven VSMC hyperplasia in the injured vessels. Overall design: Hsp60 normal vs knockout with TNF-alpha treatment
Publication Title
Cytosolic Hsp60 orchestrates the survival and inflammatory responses of vascular smooth muscle cells in injured aortic vessels.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Identification of intrathymic Eomes+ natural Th1 cells creates a novel idea that there is more than one way for the generation of innate CD4 T cells. To more deeply characterize this type of innate T cells, we compared the gene expression profile between nTh1 cells generated in CIITAtg mice and classic Th1 cells differentiated from naive CD4 T cells in Th1-polarizing condition.
Publication Title
Thymic low affinity/avidity interaction selects natural Th1 cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We asked whether combining Notch and VEGF blockade would enhance suppression of tumor angiogenesis and growth, using the NGP neuroblastoma model. NGP tumors were engineered to express a Notch1 decoy construct (N1D), which restricts Notch signaling, and then treated with either the anti-VEGF antibody bevacizumab or vehicle. Combining Notch and VEGF blockade led to blood vessel regression, increasing endothelial cell apoptosis and disrupting pericyte coverage of endothelial cells. Combined Notch and VEGF blockade did not affect tumor weight, but did additively reduce tumor viability. Our results indicate that Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis, and show that concurrent blockade disrupts primary tumor vasculature and viability further than inhibition of either pathway alone.
Publication Title
Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Prdx2 is the thioredoxin-dependent peroxidase that reduces H2O2 using reducing power NADPH in the presence of thioredoxin and thioredoxin reductase. Prdx2 plays an important role in growth. factor signaling in mammlian cells. Therefore, we examined the gene expression in colon adenocarcinoma cell line HT29 after Prdx2 depletion. Prdx2 depletion resulted in a significant alteration on gene expression, including protein synthesis, metabolisms, and cell cycle. Overall design: Control-siRNA-transfected versus PRDX2-siRNA-transfected HT29 and SW480 cells
Publication Title
Interaction of tankyrase and peroxiredoxin II is indispensable for the survival of colorectal cancer cells.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- NextSeq 500
Description
To identify the molecular mechanisms responsible for enhanced atopic dermatitis (AD) pathogenesis upon Ets1 deficiency in CD4+ T cells, we compared transcriptome profile between CD4+ T cells from littermate control (LMC) and Ets1?dLck mice at the peak of AD progression by performing RNA-seq. Overall design: Skin-draining lymph nodes near sites of inflammation under AD were excised from LMC and Ets1?dLck mice and prepared into single cell suspensions. CD4+ T cells were purified by CD4+ negative selection method.
Publication Title
Ets1 suppresses atopic dermatitis by suppressing pathogenic T cell responses.
Sample Metadata Fields
Cell line, Subject
View Samples