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Homo sapiens
34 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
EGF and HRG, growth factor ligands for EGFR and ErbB3/4 receptor, induce transient and sustained ERK activity associated with cellular proliferation and differentiation of MCF-7 cells, respectively. To rigorously analyze the effect of ERK signal duration for mRNA expression dynamics and its relationship with cell determination, we modified the EGF-triggered ERK signal duration by changing the EGFR activation dynamics by impairing the ubiquitination and degradation process. Mutation of the six lysine residues (6KR; K692, K713, K730, K843, K905 and K946) of the EGFR responsible for ubiquitin conjugation has shown sustained phosphorylation of the receptor (Huang et al, 2006; Goh et al, 2010). Therefore we constructed the MCF-7 cell lines that stably express 6KR EGFR (6KR), and analyzed signaling and mRNA expression dynamics in response to EGF and HRG.
Publication Title
Feedforward regulation of mRNA stability by prolonged extracellular signal-regulated kinase activity.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Cell line, Race, Time
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GSE13009- Homo sapiens
- 68 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Sharing common ErbB/HER receptor signaling pathway, heregulin (HRG) induces differentiation of MCF-7 breast cancer cells while epidermal growth factor (EGF) elicits proliferation. Although the cell fate led by those two ligands was totally different, the gene expression profile in early transcription was unexpectedly qualitatively similar, suggesting that the gene expression in late transcription, not early transcription, may reflect a respect of ligand specificity. In this study, based on the data from time-course microarray of all human genes, we predicted and determined a series of transcription factors which may control HRG-specific timed-late transcription and cellular differentiation of MCF-7 cells. Validation analyses showed that one of activator protein 1 (AP-1) families appeared just after c-Fos expression, another AP-1 family partner, induced expression of another transcription factor through activation of AP-1 complex. Furthermore, expression of this transcription factors caused suppression of extracellular signal-regulated kinase (ERK) phosphorylation which is sustainedly regulated by HRG-initiated ErbB signaling. Overall, our analysis indicated an importance of formation of timed-transcriptional regulatory network and its function to control upstream signaling pathway through negative feedback for cellular differentiation.
Publication Title
Ligand-specific sequential regulation of transcription factors for differentiation of MCF-7 cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 142 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Quantitative phosphoproteome and transcriptome analysis of ligand-stimulated MCF-7 human breast cancer cells was performed to understand the mechanisms of tamoxifen resistance at a systems level. Phosphoproteome data revealed that wild type (WT) cells were more enriched with phospho-proteins than tamoxifen-resistant (TamR) cells after stimulation with ligands. Surprisingly, decreased phosphorylation after ligand perturbation was more common than increased phosphorylation. In particular, 17beta-estradiol (E2) induced down-regulation in WT cells at a very high rate. E2 and the ErbB ligand, heregulin (HRG) induced almost equal numbers of up-regulated phospho-proteins in WT cells. Pathway and motif activity analyses using transcriptome data additionally suggested that deregulated activation of GSK3B(glycogen synthase kinase 3 beta) and MAPK1/3 signaling might be associated with altered activation of CREB and AP-1 transcription factors in TamR cells and this hypothesis was validated by reporter assays. An examination of clinical samples revealed that, inhibitory phosphorylation of GSK3B at serine 9 was significantly lower in tamoxifen-treated breast cancer patients that eventually had relapses, implying that activation of GSK3B may be associated with the tamoxifen resistant phenotype. Thus, the combined phosphoproteome and transcriptome dataset analyses revealed distinct signal-transcription programs in tumor cells and provided a novel molecular target to understand tamoxifen resistance.
Publication Title
Integrated quantitative analysis of the phosphoproteome and transcriptome in tamoxifen-resistant breast cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Cell line, Treatment, Race, Time
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Mouse Promoter 1.0R Array (mmprompr)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 23 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Mouse Promoter 1.0R Array (mmprompr)
Description
Immunological memory is generally thought to be mediated exclusively by lymphocytes such as memory T and B cells. However, enhanced innate immune responses caused by a previous infection increase protection against reinfection suggesting the presence of innate immunological memory. Here, we describe expression profile of peritoneal macrophages from wild-type mice pre-administrated with TLR ligands or from ATF7 knockout mice. ATF7 suppresses a group of innate-immunity genes in macrophage by recruiting H3K9 dimethyltransferase G9a. TLR ligands induce ATF7 phosphorylation, leading to release of ATF7 from chromatin and reduction in H3K9me2 level. Partially disrupted chromatin structure and increased basal expression on target genes are maintained for a long period, increasing resistance pathogens. Therefore we speculate ATF7 is important factor in controlling innate immunological memory.
Publication Title
The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The activation signaling of transcription factor nuclear factor-kB (NF-kB) plays central role for immune system. One of key kinase mediating this pathway is TAK1 in adaptive and innate immunity.
Publication Title
Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-κB activation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HiSeq 3000
Description
The aim of this research is to uncover the molecular mechanisms of how Regnase-1 degrades cytokine mRNAs. Inflammation is mediated by proinflammatory cytokines and cytokine expression is tightly regulated in innate immune cells such as macrophages and dendritic cells controlling their activation and maturation. Cytokine mRNA expression is controlled at both transcriptional and post-transcriptional levels, and post-transcriptional damping of cytokine expression is a critical step for resolution of inflammation and prevention of unintended tissue damage. However, the mechanisms of RNA metabolism in immune system is not clear. Thus, the aim of this research project is to investigate the molecular mechanisms of RNA metabolism by Regnase-1 in immune system.
Publication Title
Translation-dependent unwinding of stem-loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 23 Downloadable Samples
- Illumina HiSeq 1500
Description
Virus infection induces T follicular helper (TFH) and T helper 1 (TH1) cells. Although TFH cells are important in anti-viral humoral immunity, the role of TH 1 cells is still elusive. IgG2 antibodies predominate in the response to vaccination with inactivated Influenza A virus (IAV) and were responsible for protective immunity to lethal challenge with pathogenic H5N1 and pandemic H1N1 IAVs even in mice lacking TFH cells owing to B or T cell-specific ablation of the Bcl6. We demonstrate that IL-21 and IFN-? secreted from TH1 cells were essential for greater persistence and higher titers of IgG2 protective antibodies. These results suggest that TH1 induction could be a promising strategy to induce effective neutralizing antibodies against emerging influenza viruses. Overall design: TH1 or TFH cells of wild type (WT) and conditional Bcl6-/- mice were sorted and analyzed the transcriptome using Illumina HiSeq1500.
Publication Title
Protective neutralizing influenza antibody response in the absence of T follicular helper cells.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We established two clones of induced pluripotent stem cells (iPSC) with the presenilin 2 mutation, N141 (PS2-1 iPSC and PS2-2 iPSC) by retroviral transduction of primary human fibroblasts. To show the similarity among 201B7 iPSC, PD01-25 iPSC(Sporadic Parkinson's disease patient derived iPSC), PS2-1 iPSC, PS2-2 iPSC, this experiment was designed.
Publication Title
Modeling familial Alzheimer's disease with induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BackgroundAcute coronary syndrome (ACS) is sometimes accompanied by accelerated coagulability, lipid metabolism, and inflammatory responses, which are not attributable to the cardiac events alone. We hypothesized that the liver plays a pivotal role in the pathophysiology of ACS. We simultaneously analyzed the gene expression profiles of the liver and heart during acute myocardial ischemia in mice.
Publication Title
Altered hepatic gene expression profiles associated with myocardial ischemia.
Sample Metadata Fields
Sex, Specimen part
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