Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional responses of wild-type and Gcn2-/- Th17 cells to halofuginone and rapamycin

ABSTRACT: This study was designed to evaluate similarities and differences between transcriptional responses of developing Th17 cells to the prolyl-tRNA synthetase inhibitor, halofuginone, and the mTOR inhibitor, rapamycin. Further comparisons between wild-type and Gcn2-/- Th17 cells allow for investigation into which gene modules regulated by halofuginone or rapamycin treatment require Gcn2. Murine CD4+ CD25- T cells were magnetically isolated from wild-type or Gcn2-/- T cells. These cells were activated through anti-CD3/ anti-CD28 antibodies and polarized into Th17 cells using TGFb plus IL-6. 10 nM halofuginone, 10 nM rapamycin, or vehicle control (DMSO) were added to cultures at the time of activation. Cells were harvested at 4, 18, or 72 hours post-activation and differentiation. RNA was isolated from each sample and used for microarray analysis. Each culture condition and time-point was repeated twice in independent experiments using cells isolated from different wild-type or Gcn2-/- mice. Vehicle versus halofuginone, vehicle versus rapamycin, halofuginone versus rapamycin. Gcn2-/- versus wild-type T cells treated with vehicle, halofuginone, or rapamycin.

ORGANISM(S): Mus musculus

SUBMITTER: Scott Davis

PROVIDER: E-GEOD-47478 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Transcriptional responses of wild-type and Gcn2-/- Th17 cells to halofuginone and rapamycin

Project description:This study was designed to evaluate similarities and differences between transcriptional responses of developing Th17 cells to the prolyl-tRNA synthetase inhibitor, halofuginone, and the mTOR inhibitor, rapamycin. Further comparisons between wild-type and Gcn2-/- Th17 cells allow for investigation into which gene modules regulated by halofuginone or rapamycin treatment require Gcn2.

2014-05-29 | GSE47478 | GEO

Induction and molecular signature of pathogenic Th17 cells

Project description:TGF-beta3 produced by developing Th17 cells induces highly pathogenic T cells that are functionally and molecularly distinct from TGF-beta1-induced Th17 cells. The microarray data represent a distinct molecular signature for pathogenic versus non-pathogenic Th17 cells. Total of seven groups with two to four samples per group from two independent experiments. The no cytokines group (Th0) was used as a control to normalize the data. 7 groups: B6: (IL-1beta, IL-6) B623: (IL-1beta, IL-6, IL-23) T16: (TGF-beta1, IL-6) T1623: (TGF-beta1, IL-6, IL-23) T36: (TGF-beta3, IL-6) T3623: (TGF-beta3, IL-6, IL-23) NOCYTO: no cytokines

2012-09-01 | E-GEOD-39820 | biostudies-arrayexpress

Role of mTOR in regulating the extra cellular matrix

Project description:Explored the potential role of mTOR in regulating the extra cellular matrix of TGF-b1-stimulated IPF fibroblasts grown under macromolecular crowding conditions in the presence of either CZ415 or rapamycin

2018-11-04 | PXD010164 | Pride

Expression and functions of long noncoding RNAs during human T helper cell differentiation

Project description:To improve our understanding of lncRNA expression in T cells, we used whole genome sequencing (RNA-seq) to identify lncRNAs expressed in human T cells and those selectively expressed in T cells differentiated under TH1, TH2, or TH17 polarizing conditions. The majority of these lineage-specific lncRNAs are co-expressed with lineage-specific protein-coding genes. These lncRNAs are predominantly intragenic with co-expressed protein-coding genes and are transcribed in sense and antisense orientations with approximately equal frequencies. Further, genes encoding TH lineage specific mRNAs are not randomly distributed across the genome but are highly enriched in the genome in genomic regions also containing genes encoding TH lineage-specific lncRNAs. Our analyses also identify a cluster of antisense lncRNAs transcribed from the RAD50 locus that are selectively expressed under TH2 polarizing conditions and co-expressed with IL4, IL5 and IL13 genes. Depletion of these lncRNAs via selective siRNA treatment demonstrates the critical requirement of these lncRNAs for expression of the TH2 cytokines, IL-4, IL-5 and IL-13. Collectively, our analyses identify new lncRNAs expressed in a TH lineage specific manner and identify a critical role for a cluster of lncRNAs for expression of genes encoding TH2 cytokines. Human peripheral blood mononuclear cells (PBMC) were cultured under TH1, TH2, and TH17 polarizing conditions. TH1, TH2, and TH17 primary and effector cultures were isolated and poly(A)+ and total RNA sequencing performed.

2015-04-23 | E-GEOD-66261 | biostudies-arrayexpress

Enhanced Pathogenicity of Th17 cells Generated in the Absence of Transforming Growth Factor-β Signaling

Project description:CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1-4. Crucial for T helper17 (Th17) cells in vivo5,6, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification7-10. Herein, we show that Th17 differentiation occurs in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+Rorγt+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-β1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies. Mouse T helper 17 cell differentiation with or without TGFB

2010-08-31 | E-GEOD-23505 | biostudies-arrayexpress

Mus musculus

Project description:Transcriptional responses of wild-type and Gcn2-/- Th17 cells to halofuginone and rapamycin

| PRJNA205835 | ENA

Chemical Inhibition of the ROR?t-dependent Transcriptional Network in Th17 cells [RNA-Seq]

Project description:ROR?t is a transcription factor required for T helper 17 (Th17) cell development. We identified three ROR?t-specific inhibitors that suppress Th17 cell responses including Th17 cell-mediated autoimmune disease. We systemically characterized ROR?t binding data in the presence and absence of drug with corresponding whole-transcriptome sequencing for wild-type and ROR?t-deficient cells. ROR?t is central in a densely interconnected regulatory network, acting both as a direct activator of genes important for Th17 cell differentiation and as a direct repressor of genes from other T-cell lineages. The three inhibitors identified here reversed both of these modes of action, but to varying extents and through distinct mechanisms. Whereas one inhibitor displaced ROR?t from its target-loci, the two more potent inhibitors affected transcription predominantly without removing DNA-binding. Our work illustrates the power of a system-scale analysis of transcriptional regulation to characterize potential therapeutic compounds that inhibit pathogenic Th17 cells and suppress autoimmunity. Transcriptional profiling of Th17 cells under chemical perturbations of ROR?t, DMSO, and knockout of ROR?t

2014-04-17 | E-GEOD-56018 | biostudies-arrayexpress

Chemical Inhibition of the RORγt-dependent Transcriptional Network in Th17 cells [ChIP-Seq]

Project description:RORγt is a transcription factor required for T helper 17 (Th17) cell development. We identified three RORγt-specific inhibitors that suppress Th17 cell responses including Th17 cell-mediated autoimmune disease. We systemically characterized RORγt binding data in the presence and absence of drug with corresponding whole-transcriptome sequencing for wild-type and RORγt-deficient cells. RORγt is central in a densely interconnected regulatory network, acting both as a direct activator of genes important for Th17 cell differentiation and as a direct repressor of genes from other T-cell lineages. The three inhibitors identified here reversed both of these modes of action, but to varying extents and through distinct mechanisms. Whereas one inhibitor displaced RORγt from its target-loci, the two more potent inhibitors affected transcription predominantly without removing DNA-binding. Our work illustrates the power of a system-scale analysis of transcriptional regulation to characterize potential therapeutic compounds that inhibit pathogenic Th17 cells and suppress autoimmunity. DNA binding of RORγt in WT Th17 cells and under chemical perturbations of RORγt; Additional data is included for epitope-tagged exogenous RORγt in EL4 cells (a murine lymphoma cell line)

2014-04-17 | E-GEOD-56019 | biostudies-arrayexpress

Interleukin-23-induced transcription factor Blimp1 promotes pathogenicity of T helper 17 cells

Project description:Interleukin-23 (IL-23) is a pro-inflammatory cytokine required for the pathogenicity of T helper 17 (Th17) cells but the molecular mechanisms governing this process remain unclear. We identified the transcription factor Blimp-1 (Prdm1) as a key IL-23-induced factor that drove the inflammatory function of Th17 cells. In contrast to thymic deletion of Blimp-1, which causes T cell development defects and spontaneous autoimmunity, peripheral deletion of this transcription factor resulted in reduced Th17 activation and reduced severity of autoimmune encephalomyelitis. Furthermore, genome wide occupancy and overexpression studies in Th17 cells revealed that Blimp-1 co-localized with transcription factors RORÎ³t, STAT-3 and p300 at the Il23r, Il17a/f and Csf2 cytokine loci to enhance their expression. Blimp-1 also directly bound to and repressed cytokine loci Il2 and Bcl6. Taken together, our results demonstrate that Blimp-1 is an essential transcription factor downstream of IL-23 that acts in concert with RORÎ³t to activate the Th17 inflammatory program. Genome-wide binding analysis of Blimp1 from in vitro generated T effector and regulatory cells

2016-06-15 | E-GEOD-75724 | biostudies-arrayexpress

Chemical Inhibition of the RORγt-dependent Transcriptional Network in Th17 cells [RNA-Seq 2]

Project description:RORγt is a transcription factor required for T helper 17 (Th17) cell development. We identified three RORγt-specific inhibitors that suppress Th17 cell responses including Th17 cell-mediated autoimmune disease. We systemically characterized RORγt binding data in the presence and absence of drug with corresponding whole-transcriptome sequencing for wild-type and RORγt-deficient cells. RORγt is central in a densely interconnected regulatory network, acting both as a direct activator of genes important for Th17 cell differentiation and as a direct repressor of genes from other T-cell lineages. The three inhibitors identified here reversed both of these modes of action, but to varying extents and through distinct mechanisms. Whereas one inhibitor displaced RORγt from its target-loci, the two more potent inhibitors affected transcription predominantly without removing DNA-binding. Our work illustrates the power of a system-scale analysis of transcriptional regulation to characterize potential therapeutic compounds that inhibit pathogenic Th17 cells and suppress autoimmunity. Transcriptional profiling of Th17 cells under chemical perturbations of RORγt, DMSO, and knockout of RORγt. It includes repeats for all the data in GSE56018, plus one additional condition.

2014-04-17 | E-GEOD-56240 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data