Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Homeostasis and transitional activation of regulatory T cells require c-Myc

ABSTRACT: Homeostasis and transitional activation of regulatory T cells require c-Myc

PROVIDER: PRJNA593657 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Homeostasis and transitional activation of regulatory T cells require c-Myc

Project description:Regulatory T (Treg) cell activation and expansion during neonatal life and in response to inflammation are critical for immunosuppression, yet the mechanisms governing these events are incompletely understood. We report that the oncogene and transcriptional regulator c-Myc (Myc) controls immune homeostasis through regulation of Treg cell accumulation and functional activation. Myc activity is enriched in Treg cells generated during neonatal life and responding to inflammation. Myc-deficient Treg cells show cell-intrinsic defects in overall accumulation and ability to transition to an activated state during early life or acute inflammation. Consequently, loss of Myc in Treg cells results in a rapid, early-onset autoimmune disorder accompanied by uncontrolled effector CD4+ and CD8+ T cell responses. We also provide evidence that Myc regulates mitochondrial oxidative metabolism but is dispensable for fatty acid oxidation (FAO). Indeed, Treg cell-specific deletion of Cox10, which is required for oxidative phosphorylation, but not Cpt1a, the rate-limiting enzyme for FAO, results in impaired Treg cell function and maturation. Thus, Myc coordinates Treg cell accumulation, transitional activation and metabolic programming to orchestrate immune homeostasis. We used microarrays to compare the global transcription profiles of WT and Myc-null Treg cells.

2020-01-10 | GSE141499 | GEO

Homeostasis and transitional activation of regulatory T cells require c-Myc.

Project description:Regulatory T cell (Treg) activation and expansion occur during neonatal life and inflammation to establish immunosuppression, yet the mechanisms governing these events are incompletely understood. We report that the transcriptional regulator c-Myc (Myc) controls immune homeostasis through regulation of Treg accumulation and functional activation. Myc activity is enriched in Tregs generated during neonatal life and responding to inflammation. Myc-deficient Tregs show defects in accumulation and ability to transition to an activated state. Consequently, loss of Myc in Tregs results in an early-onset autoimmune disorder accompanied by uncontrolled effector CD4+ and CD8+ T cell responses. Mechanistically, Myc regulates mitochondrial oxidative metabolism but is dispensable for fatty acid oxidation (FAO). Indeed, Treg-specific deletion of Cox10, which promotes oxidative phosphorylation, but not Cpt1a, the rate-limiting enzyme for FAO, results in impaired Treg function and maturation. Thus, Myc coordinates Treg accumulation, transitional activation, and metabolic programming to orchestrate immune homeostasis.

| S-EPMC6938709 | biostudies-literature

T cell homeostasis and antitumor function require the Na+-K+-ATPase

Project description:T cell homeostasis and antitumor function require the Na+-K+-ATPase

| PRJNA1013809 | ENA

Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis

Project description:Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis

| PRJNA607766 | ENA

Immune homeostasis and regulation of the Interferon pathway require myeloid-derived Regnase-3

Project description:Immune homeostasis and regulation of the Interferon pathway require myeloid-derived Regnase-3

| PRJNA530962 | ENA

Congenital T cell activation blocks transitional to follicular B cell maturation in humans

Project description:In patients with CTLA4 deficiency, CD40L-expressing T cells inhibit transitional to follicular B cell maturation in the T cell zone of lymph nodes through the induction of mTORC1 signaling in transitional B cells. We apply scRNA-seq to identify upregulation of PI3K, mTORC1, and oxidative phosphorylation pathways in patients with CTLA4 deficiency, and to characterize resolution of follicular block after treatment with abatacept.

2021-11-10 | GSE188449 | GEO

Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis (RNA-Seq).

Project description:Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis (RNA-Seq).

| PRJNA607769 | ENA

Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis (ChIP-Seq).

Project description:Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis (ChIP-Seq).

| PRJNA607770 | ENA

PRPS activity governs redox homeostasis in MYC-driven lymphoma

Project description:Myc hyperactivation coordinately regulates numerous metabolic processes to drive lymphomagenesis. However, the temporal and epistatic relationships between the medley of pathways, factors, and mechanisms that must functionally cooperate to preserve homeostasis in Myc-overexpressing cells remain largely unknown. Here, we characterize the earliest metabolic alterations upon induction of oncogenic Myc and pinpoint the major determinants of redox balance in Myc-overexpressing lymphomas. We find that Myc rapidly stimulates the oxidative pentose phosphate pathway (oxPPP), nucleic acid synthesis, and mitochondrial respiration, which collectively steers cellular equilibrium to a more oxidative state. Acting at the nexus of these processes, we identify Myc-dependent hyperactivation of the phosphoribosyl pyrophosphate synthetase (PRPS) enzyme as the primary regulator of redox status in lymphoma cells. Mechanistically, Myc induces expression of the allosteric feedback refractory PRPS2 isozyme, thereby remodeling the PRPS enzyme complex to a more active state that efficiently funnels ribose-5-phosphate from the PPP to downstream nucleotides. Genetic inactivation of PRPS2 increases oxPPP flux and futile cycling, leading to increased NADPH levels and reductive stress-mediated cell death. Employing a pharmacological screen in wild-type, PRPS1- or PRPS2-knockout lymphoma cells to reveal cooperative functional interactions, we discovered that cells engineered to lack PRPS1 or PRPS2 displayed opposing differential sensitivities to compounds targeting the glutathione and thioredoxin systems, outlining effective rational combinatorial therapeutic approaches in Myc-driven lymphomas. Collectively, our work unravels how the activity of one critical node amongst the expansive metabolic architecture of a cell can be tuned by an oncogenic pathway to alter redox homeostasis and create new exploitable dependencies

2025-02-20 | GSE282435 | GEO

Proteome profiling upon Myc activation

Project description:The effect of Myc activation on the proteome was investigated in U2OS cells and proteome changes were combined with Ribo-seq, RNA-seq and GRO-seq analyses.

2015-11-09 | PXD002073 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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