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GSE28642
Homo sapiens
4 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A synthetic analog of sphingosine named FTY720 (Fingolimod), phosphorylated by sphingosine kinase-2, interacts with sphingosine-1-phosphate (S1P) receptors expressed on various cells. FTY720 suppresses the disease activity of multiple sclerosis (MS) chiefly by inhibiting S1P-dependent egress of autoreactive T lymphocytes from secondary lymphoid organs, and possibly by exerting anti-inflammmatory and neuroprotective effects directly on brain cells. However, at present, biological effects of FTY720 on human microglia are largely unknown. We studied FTY720-mediated apoptosis of a human microglia cell line HMO6. The exposure of HMO6 cells to non-phosphorylated FTY720 (FTY720-non-P) induced apoptosis in a dose-dependent manner with IC50 of 10.62.0 microM, accompanied by the cleavage of caspase-7 and caspase-3 but not of caspase-9. The apoptosis was inhibited by Z-DQMD-FMK, a caspase-3 inhibitor, but not by Pertussis toxin, a Gi protein inhibitor, suramin, a S1P3/S1P5 inhibitor, or W123, a S1P1 competitive antagonist, although HMO6 expressed S1P1, S1P2, and S1P3. Furthermore, both phosphorylated FTY720 (FTY720-P) and SEW2871, a S1P1 selective agonist did not induce apoptosis of HMO6. Genome-wide gene expression profiling and molecular network analysis indicated activation of transcriptional regulation by sterol regulatory element-binding protein (SREBP) in FTY720-non-P-treated HMO6 cells. Western blot verified activation of SREBP2 in these cells, and apoptosis was enhanced by pretreatment with simvastatin, an activator of SREBP2, and by overexpression of the N-terminal fragment of SREBP2. These observations suggest that FTY720-non-P-induced apoptosis of HMO6 human microglia is independent of S1P receptor binding, and positively regulated by the SREBP2-dependent proapoptotic signaling pathway.
Publication Title
Non-phosphorylated FTY720 induces apoptosis of human microglia by activating SREBP2.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals is proclaimed to have value-added clinical potential in the regeneration of complex cell types like cardiomyocytes. Despite the availability of several small molecule inhibitors capable of modulating specific receptor-ligand interaction or enzymatic activity, no bioactive synthetic DNA-binding inhibitor targeting key cell fate-controlling gene like SOX2 is available yet. Herein, we demonstrate a novel DNA-based chemical approach to guide hiPSCs differentiation using pyrrole-imidazole polyamides (PIPs), which are sequence-selective DNA-binding synthetic molecules. Harnessing the knowledge about key transcriptional changes associated with cardiomyocyte induction, we developed a PIP termed SOX-L targeting 5-CTTTGTT-3 sequence and demonstrate the inhibition of SOX2-DNA interaction and mesoderm induction of hiPSCs. Genome-wide gene analyses revealed that SOX-L remarkably specified cardiac mesoderm by triggering targeted alteration in SOX2-associated gene regulatory networks. Also, employment of SOX-L along with a Wnt inhibitor successfully generated spontaneously contracting cardiomyocytes to validate our concept that DNA-binding inhibitors like PIPs could be used for directed differentiation of hiPSCs. Because PIPs could be fine-tuned to target specific DNA sequences, our DNA-based approach could be expanded to directly target and distinctively regulate key transcription factor associated with the desired cell type.
Publication Title
A synthetic DNA-binding inhibitor of SOX2 guides human induced pluripotent stem cells to differentiate into mesoderm.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 82 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of this study is to identify responders to FOLFOX therapy by applying the Random Forests (RF) algorithm to gene expression data. Eighty-three unresectable colorectal cancer (CRC) patients including 42 responders and 41 non-responders were divided into training (54 patients) and test (29 patients) sets.
Publication Title
Potential responders to FOLFOX therapy for colorectal cancer by Random Forests analysis.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Spatial Interplay between Polycomb and Trithorax Complexes Controls Transcriptional Activity in T Lymphocytes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina HiSeq 1500, Illumina HiSeq 2500
Description
Trithorax group (TrxG) and Polycomb group (PcG) proteins are two mutually antagonistic chromatin modifying complexes, however, how they together mediate transcriptional counterregulation remains unknown. Genome-wide analysis revealed that binding of Ezh2 and Menin, central members of the PcG and TrxG complexes, respectively, were reciprocally correlated. Moreover, we identified a developmental change in the positioning of Ezh2 and Menin in differentiated T lymphocytes compared to embryonic stem cells. Ezh2-binding upstream and Menin-binding downstream of the transcription start site (TSS) was frequently found at genes with higher transcriptional levels, and Ezh2-binding downstream and Menin-binding upstream was found at genes with lower expression in T lymphocytes. Interestingly, of the Ezh2 and Menin co-occupied genes, those exhibiting occupancy at the same position displayed greatly enhanced sensitivity to loss of Ezh2. Finally, we also found that different combinations of Ezh2 and Menin occupancy were associated with expression of specific functional gene groups important for T cell development. Therefore, spatial cooperative gene regulation by the PcG and TrxG complexes may represent a novel mechanism regulating the transcriptional identity of differentiated cells. Overall design: Gene expression profiles of ES cells, B cells and T cells are assessed by RNA-seq.
Publication Title
Spatial Interplay between Polycomb and Trithorax Complexes Controls Transcriptional Activity in T Lymphocytes.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Pyrrole-imidazole polyamides (PIPs) have been shown to inhibit gene expression by interrupting the DNA-protein interface. Human Ectopic viral integration site 1 (EVI1) is an oncogenic transcription factor which plays a key role in many aggressive forms of cancer. We have developed a novel pyrroleimidazole polyamide, PIP1 targeting the REL/ELK1 binding site in the EVI1 minimal promoter that can significantly repress the expression of EVI1 in MDA-MB-231 cells. Whole-transcriptome analysis revealed that a fraction of EVI1-driven genes were modulated by PIP1.
Publication Title
Targeted suppression of EVI1 oncogene expression by sequence-specific pyrrole-imidazole polyamide.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Trithorax group (TrxG) and Polycomb group (PcG) proteins are two mutually antagonistic chromatin modifying complexes, however, how they together mediate transcriptional counterregulation remains unknown. Genome-wide analysis revealed that binding of Ezh2 and Menin, central members of the PcG and TrxG complexes, respectively, were reciprocally correlated. Moreover, we identified a developmental change in the positioning of Ezh2 and Menin in differentiated T lymphocytes compared to embryonic stem cells. Ezh2-binding upstream and Menin-binding downstream of the transcription start site (TSS) was frequently found at genes with higher transcriptional levels, and Ezh2-binding downstream and Menin-binding upstream was found at genes with lower expression in T lymphocytes. Interestingly, of the Ezh2 and Menin co-occupied genes, those exhibiting occupancy at the same position displayed greatly enhanced sensitivity to loss of Ezh2. Finally, we also found that different combinations of Ezh2 and Menin occupancy were associated with expression of specific functional gene groups important for T cell development. Therefore, spatial cooperative gene regulation by the PcG and TrxG complexes may represent a novel mechanism regulating the transcriptional identity of differentiated cells.
Publication Title
Spatial Interplay between Polycomb and Trithorax Complexes Controls Transcriptional Activity in T Lymphocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Series of samples studying effect of knock out Emx2 in urogenital epithelium of mouse embryos at E10.5.
Publication Title
Abnormal epithelial cell polarity and ectopic epidermal growth factor receptor (EGFR) expression induced in Emx2 KO embryonic gonads.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Colon cancer invade to depper layer and the expression of major molecules at cancer front change. But the screening of expression changing at cancer front has not be adequtely clarified.
Publication Title
Microarray Analysis of Gene Expression at the Tumor Front of Colon Cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Oryza sativa indica group
- 17 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Rice deletion mutants have not been widely used in functional genomics, because the mutated genes are not tagged and therefore, difficult to identify
Publication Title
Detection of genomic deletions in rice using oligonucleotide microarrays.
Sample Metadata Fields
Specimen part
View Samples