Browse
Submit Data
Databases
API
Help

Dataset Information

0 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE47478 | GEO | 2014/05/29

SECONDARY ACCESSION(S): PRJNA205835

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

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. 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.

2014-05-29 | E-GEOD-47478 | biostudies-arrayexpress

Discordant regulation of eIF2 kinase GCN2 and mTORC1 during nutrient stress

Project description:Here we report Total RNA seq and RiboSeq on MEF cells treated with halofuginone. Halofuginone is a competitive inhibitor of the Prolyl-tRNA synthetase that results in an accumulation of uncharged Prolyl-tRNA upon treatment that leads to an activation of the protein kinase Gcn2.

2021-05-26 | GSE156850 | GEO

Halofuginone, a tRNA-synthetase inhibitor, decreases bulk protein synthesis independently of the integrated stress response

Project description:The integrated stress response (ISR), a vital homeostatic pathway, is an emerging therapeutic target for a broad range of clinical indications. Halofuginone (HF) is a phase 2 clinical compound that induces the ISR by inhibiting the glutamyl-prolyl-tRNA synthetase (EPRS). Here we report that although HF induces the predicted canonical ISR adaptations consisting of attenuation of protein synthesis and gene expression reprogramming, the former surprisingly occurs independently of GCN2 and eIF2 phosphorylation. Proline supplementation rescues the observed HF-induced changes indicating that they result from an on-target effect due to inhibition of EPRS. We find that attenuation of translation initiation through GCN2-to-eIF2 signaling is not robust enough to prevent translation elongation defects caused by HF. Exploiting this vulnerability, we show that cancer cells presenting an increased proline dependency are sensitized to HF. This work provides novel insights on ISR signaling and a molecular framework to guide the targeted development of HF.

2022-04-27 | PXD028744 | Pride

Transcription profiling of mouse T cells treated with halofuginone to investigate regulation of Y cell gene expression by Halofuginone (HF)

Project description:T cell differentiation to the Th17 effector subset requires stimulation through the T cell and co-stimulatory receptors, together with cytokine stimulation by TGFb and IL-6. The small molecule halofuginone (HF) inhibits Th17 cell development and induces a pattern of stress-regulated gene expression that mimics amino acid starvation. We used global transcript profiling to ask how halofuginone modulates gene expression induced during T cell activaiton and Th17 differentiation Experiment Overall Design: Purified mouse CD4+ CD25- T cells were activated under Th17 polarizing cytokine conditions and treated with either halofuginone or its inactive derivative, MAZ1310, for 3- or 6-hours.

2009-04-19 | E-GEOD-15624 | biostudies-arrayexpress

Halofuginone is a potent inhibitor of SARS-CoV-2 Infection and Replication [Exp3]

Project description:Here we identify halofuginone, a Prolyl-tRNA Synthetase (PRS) inhibitors as a potent inhibitors of SARS-CoV-2 cellular entry and viral replication. To infect the host cell, the SARS-CoV-2 spike protein interacts with cell surface heparan sulfate (HS) and angiotensin-converting enzyme 2 (ACE2) through its Receptor Binding Domain. Removal of cell surface HS or blockade of HS biosynthesis represents a promising clinical target for treatment of SARS-CoV-2. In vitro studies confirm that halofuginone and PRS inhibitors prevent HS biosynthesis and thereby HS cell surface presentation and Spike protein binding. Halofuginone also suppresses authentic SARS-CoV-2 infection by inhibiting PRS activity, which decreases the translation efficiency of proline-rich HS biosynthetic enzymes and essential SARS-CoV-2 proteins after infection. Thus, halofuginone inhibits SARS-CoV-2 at both attachment and post-entry steps and blocks SARS-CoV-2 infection of human lung airway epithelial cells at low nanomolar concentrations. These findings support the use of halofuginone, an orally bioavailable anti-fibrotic and anti-inflammatory compound with encouraging clinical phase 1 safety data, as an antiviral drug to prevent SARS-CoV-2 infection.

2023-08-28 | GSE166411 | GEO

Halofuginone is a potent inhibitor of SARS-CoV-2 Infection and Replication [Exp2]

Project description:Here we identify halofuginone, a Prolyl-tRNA Synthetase (PRS) inhibitors as a potent inhibitors of SARS-CoV-2 cellular entry and viral replication. To infect the host cell, the SARS-CoV-2 spike protein interacts with cell surface heparan sulfate (HS) and angiotensin-converting enzyme 2 (ACE2) through its Receptor Binding Domain. Removal of cell surface HS or blockade of HS biosynthesis represents a promising clinical target for treatment of SARS-CoV-2. In vitro studies confirm that halofuginone and PRS inhibitors prevent HS biosynthesis and thereby HS cell surface presentation and Spike protein binding. Halofuginone also suppresses authentic SARS-CoV-2 infection by inhibiting PRS activity, which decreases the translation efficiency of proline-rich HS biosynthetic enzymes and essential SARS-CoV-2 proteins after infection (data not provided here). Thus, halofuginone inhibits SARS-CoV-2 at both attachment and post-entry steps and blocks SARS-CoV-2 infection of human lung airway epithelial cells at low nanomolar concentrations. These findings support the use of halofuginone, an orally bioavailable anti-fibrotic and anti-inflammatory compound with encouraging clinical phase 1 safety data, as an antiviral drug to prevent SARS-CoV-2 infection.

2023-08-28 | GSE157034 | GEO

Halofuginone is a potent inhibitor of SARS-CoV-2 Infection and Replication [Exp1]

Project description:Here we identify halofuginone, a Prolyl-tRNA Synthetase (PRS) inhibitors as a potent inhibitors of SARS-CoV-2 cellular entry and viral replication. To infect the host cell, the SARS-CoV-2 spike protein interacts with cell surface heparan sulfate (HS) and angiotensin-converting enzyme 2 (ACE2) through its Receptor Binding Domain. Removal of cell surface HS or blockade of HS biosynthesis represents a promising clinical target for treatment of SARS-CoV-2. In vitro studies confirm that halofuginone and PRS inhibitors prevent HS biosynthesis and thereby HS cell surface presentation and Spike protein binding. Halofuginone also suppresses authentic SARS-CoV-2 infection by inhibiting PRS activity, which decreases the translation efficiency of proline-rich HS biosynthetic enzymes and essential SARS-CoV-2 proteins after infection (data not provided here). Thus, halofuginone inhibits SARS-CoV-2 at both attachment and post-entry steps and blocks SARS-CoV-2 infection of human lung airway epithelial cells at low nanomolar concentrations. These findings support the use of halofuginone, an orally bioavailable anti-fibrotic and anti-inflammatory compound with encouraging clinical phase 1 safety data, as an antiviral drug to prevent SARS-CoV-2 infection.

2023-08-28 | GSE157032 | GEO

Regulation of T cell gene expression by Halofuginone (HF)

Project description:T cell differentiation to the Th17 effector subset requires stimulation through the T cell and co-stimulatory receptors, together with cytokine stimulation by TGFb and IL-6. The small molecule halofuginone (HF) inhibits Th17 cell development and induces a pattern of stress-regulated gene expression that mimics amino acid starvation. We used global transcript profiling to ask how halofuginone modulates gene expression induced during T cell activaiton and Th17 differentiation Keywords: T cell activation/ differentiation timecourse

2009-04-10 | GSE15624 | GEO

Transcriptional responses to TNF following HFol treatment of wild type and GCN2 depleted synoviocytes

Project description:We report the effects of Hfol on TNF induction of inflammatory genes in wild type cells versus cells depleted of GCN2 RNA-seq analysis of wild type or GCN2-depleted established fibroblast like synoviocytes (K4 cells) treated with TNFa in the presence or absence of Halofuginone (HF).

2020-03-22 | GSE145203 | GEO