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SRP152952
Mus musculus
9 Downloadable Samples
Illumina HiSeq 2500
Description
IL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy. Overall design: Examination of DMF-induced expression changes in 3 conditions, 3 samples each: murine TC17 cells without treatment as control group, murine Tc17 cells treated with DMF and murine Tc17 cells treated with DMF and Glutathione(GSH)
Publication Title
IL-17<sup>+</sup> CD8<sup>+</sup> T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
IL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy. Overall design: CD8+ memory cells from human blood
Publication Title
IL-17<sup>+</sup> CD8<sup>+</sup> T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Caenorhabditis elegans
- 14 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: We observed protein homeostasis modulations when anc-1 is knocked-down. We wanted to measure changes in gene expression profiles following this manipulation. Methods: We treated wild type (strain N2) or polyQ35-YFP (strain AM140) nematodes, which express toxic aggregative proteins that challenge their protein homeostasis, with anc-1 RNAi until day six of adulthood, and compared their gene expression levels to those of untreated worms. Results: The knockdown of anc-1 leads to modified expression levels of hundreds of genes. There is an enrichment of transcription factors and protein homeostasis modulators, such as E3 ubiquitin ligases. Conclusions: anc-1 regulates protection from toxic aggregative proteins, at least partially, by regulating the expression of genes that encode protein homeostasis factors. Overall design: Wild type strain, three repeats; polyQ35-YFP strain, four repeats. Each repeat has two conditions: untreated (EV), and RNAi toward anc-1.
Publication Title
Gene expression modulation by the linker of nucleoskeleton and cytoskeleton complex contributes to proteostasis.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pirin (PIR) is a putative transcriptional regulator whose expression is silenced in cells bearing the AML1/ETO and PML/RAR leukemogenic fusion proteins and is significantly repressed in a large proportion of acute myeloid leukemias. PIR expression increases during in vitro myeloid differentiation of primary hematopoietic precursor cells, and ablation of PIR in the U937 myelomonocytic cell line or in murine primary hematopoietic precursor cells results in impairment of terminal myeloid differentiation.
Publication Title
Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2500
Description
Human transcripts can typically be processed at multiple polyadenylation sites to yield mRNA isoforms with distinct 3 ends. A multitude of factors contributes to the choice of individual polyadenylation sites in different cell types and tissues. In this study we have found that the heterogenous ribonucleoprotein C (hnRNP C), an RNA binding protein that was previously linked to splicing and polyadenylation at Alu repeat elements, is a general regulator of pre-mRNA cleavage and polyadenylation. By sequencing mRNA 3 ends from cells expressing normal and reduced levels of hnRNP C we found that transcripts that contain poly(U) tracts around their poly(A) sites respond in a manner indicative of hnRNP C repressing cleavage and polyadenylation. The 3 UTR isoforms whose abundance is modulated by hnRNP C contain U-rich elements and can thereby interact with A/U-rich element binding proteins that have been shown to alter transcript stability, sub-cellular localization and even the localization of the translated proteins.
Publication Title
A comprehensive analysis of 3' end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: To evaluate the presence of a gene expression signature present before treatment as predictive of response to treatment with MAGEA3
Publication Title
Predictive gene signature in MAGE-A3 antigen-specific cancer immunotherapy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The contribution of aberrant DNA methylation and the downstream effects in tumorogenesis through silencing of tumor suppressor genes (TSGs) and microRNAs has been investigated. Since these epigenetic alterations can be reversed, we investigated the effects of the epigenetic therapy in breast cancer cell lines.
Publication Title
Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.
Sample Metadata Fields
Treatment
View Samples- Escherichia coli
- 3 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Transcriptional analysis of the effects of the deletion of the sRNAs glmY and glmZ in EHEC
Publication Title
Global analysis of posttranscriptional regulation by GlmY and GlmZ in enterohemorrhagic Escherichia coli O157:H7.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The present study was designed to test the hypothesis that limited growth of the fetal liver in the model of maternal fasting is independent of well-characterized signaling mechanisms that are known to regulate somatic growth in adult animals.
Publication Title
Regulation of fetal liver growth in a model of diet restriction in the pregnant rat.
Sample Metadata Fields
Specimen part, Treatment
View Samples