Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Subset-specific mitochondrial and DNA damage shapes T cell responses to fever and inflammation

ABSTRACT: Heat is a cardinal feature of inflammation that affects enzymes and molecular complexes, yet the effects on immune cells remain uncertain. We show heat broadly increased inflammatory activity of CD4+ T cell subsets and decreased Treg suppressive function. Heat-exposed Th1 cells, however, selectively developed mitochondrial stress with elevated reactive oxygen species and DNA damage driven by dependence on electron transport chain complex 1 (ETC1), which rapidly decreased activity. While Tp53 and Sting eliminated damaged Th1 cells, those that adapted showed improved long-term activity. Th1 cells with DNA damage and ETC1 signatures were also detected in Crohn’s disease and rheumatoid arthritis. Fever-relevant heat thus selectively induces mitochondrial stress in Th1 cells that drives apoptosis or adaptation to maintain genomic integrity and improve T cell function.

ORGANISM(S): Mus musculus

PROVIDER: GSE243323 | GEO | 2024/09/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

mRNA-sequencing of thyroid cancer cell lines

Project description:A metabolic hallmark of cancer identified by Warburg is the increased consumption of glucose and secretion of lactate, even in the presence of oxygen. Although many tumors exhibit increased glycolytic activity, most forms of cancer rely on mitochondrial respiration for tumor growth. We report here that Hürthle cell carcinoma of the thyroid (HTC) models harboring mitochondrial DNA-encoded defects in complex I of the mitochondrial electron transport chain exhibit impaired respiration and alterations in glucose metabolism. CRISPR-Cas9 pooled screening identified glycolytic enzymes as selectively essential in complex I-mutant HTC cells. We demonstrate in cultured cells and a PDX model that small molecule inhibitors of lactate dehydrogenase selectively induce an ATP crisis and cell death in HTC. This work demonstrates that complex I loss exposes fermentation as a therapeutic target in HTC and has implications for other tumors bearing mutations that irreversibly damage mitochondrial respiration.

2023-04-26 | GSE230401 | GEO

Pooled CRISPR-Cas9 screens for metabolic liabilities in Hurthle cell carcinoma

2023-04-26 | GSE230399 | GEO

Fever supports CD8+ effector T cell responses by promoting mitochondrial translation

Project description:Fever can provide a survival advantage during infection. Metabolic processes are sensitive to environmental conditions, but the effect of fever on T cell metabolism is not well characterized. We show that in activated CD8+ T cells, exposure to febrile temperature (39°C) augmented metabolic activity and T cell effector functions, despite having a limited effect on proliferation or activation marker expression. Transcriptional profiling revealed an upregulation of mitochondrial pathways, which was consistent with increased mitochondrial metabolism and mass observed in T cells exposed to 39°C. Through in vitro and in vivo models we determined that mitochondrial translation is integral to the enhanced metabolic activity and function of CD8+ T cells exposed to febrile temperature. Transiently exposing donor lymphocytes to 39°C prior to infusion in a myeloid leukemia (ML) mouse model conferred enhanced therapeutic efficacy, raising the possibility that exposure of T cells to febrile temperatures could have clinical potential.

2021-07-02 | GSE171245 | GEO

Comparison of L-carnitine treated day 6 in vivo bovine embryos to controls, in both the Jersey and Holstein breeds.

Project description:The decreased rate of pregnancy obtained in cattle using frozen in vitro embryos compared to in vivo embryos has been associated with over-accumulation of intracellular lipid, which causes cell damage during cryopreservation. It is believed that the higher lipid content of blastomeres of bovine embryos produced in vitro results in darker coloured cytoplasm which could be a consequence of impaired mitochondrial function. In this study, L-carnitine was used as a treatment to reduce embryonic lipid content by increasing metabolism in cultured bovine embryos. We have observed previously that in vivo embryos of different dairy breed collected from cows housed and fed under the same conditions differed in lipid content and metabolism. As such, breed effects between Holstein and Jersey were also accounted for general appearance, lipid composition, mitochondrial activity and gene expression. Adding L-carnitine to the embryo culture medium reduced the lipid content in both breeds due to increased mitochondrial activity. L-carnitine vs controls, in 4 replicates for each breed, with dye-swaps.

2014-10-23 | E-GEOD-62595 | biostudies-arrayexpress

P2X7 signaling drives Th1 cell differentiation through metabolic reprogramming for aerobic glycolysis

Project description:This study provides evidence on the molecular mechanisms by which P2RX7 signaling promotes Th1 cell differentiation. P2RX7 induces T-bet expression and aerobic glycolysis in splenic CD4+ T cells that respond to malaria, at a time prior to Th1/Tfh polarization. Cell-intrinsic P2RX7 signaling sustains the glycolytic pathway and causes bioenergetic mitochondrial stress in activated CD4+ T cells. We also show in vitro the phenotypic similarities of Th1-polarized CD4+ T cells that do not express P2RX7 and those in which the glycolytic pathway is pharmacologically inhibited. In addition, ATP synthase blockade in vitro and the consequent inhibition of oxidative phosphorylation, which forces cells to use aerobic glycolysis, is sufficient to promote rapid CD4+ T cell proliferation and polarization to the Th1 profile in the absence of P2RX7. These data demonstrate that P2RX7-mediated metabolic reprograming for aerobic glycolysis is a key event for Th1 cell differentiation and suggest that ATP synthase inhibition is a fundamental mechanism by which P2X7 signaling induces the Th1 response.

2023-03-08 | PXD037754 | Pride

The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes [RNA-Seq]

Project description:Mitochondrial metabolites regulate the function and differentiation of leukemic and normal stem cells by affecting epigenetic marks. However, it is less understood how mitochondrial enzymes localize to the nucleus to control stem cell function. We discovered that the mitochondrial metabolic enzyme Hexokinase 2 (HK2) localizes to the nucleus in leukemic and normal hematopoietic stem cells. Overexpression of nuclear HK2 increased leukemic stem cell (LSC) properties and decreased differentiation while selective knockdown of nuclear HK2 promoted differentiation and decreased stem cell function. The nuclear localization of HK2 was phosphorylation dependent and required active import and export. Nuclear HK2 regulated LSC and differentiation independent of its enzymatic and metabolic activity. HK2 interacted with nuclear proteins that regulate chromatin openness and increased chromatin accessibilities at sites associated with the LSC+ signature and DNA damage repair. Consistent with these effects, nuclear HK2 increased repair of DNA damage and contributed to the mechanism by which LSCs resist DNA damaging agents. Thus, we describe a non-canonical mechanism by which mitochondrial enzymes regulate gene expression and stem cell function independent of their metabolic function.

2022-03-15 | GSE176103 | GEO

The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes [ChIP-Seq]

2022-03-15 | GSE176072 | GEO

The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes [ATAC-Seq]

2022-03-15 | GSE176071 | GEO

Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons

Project description:Nurr1 (Nr4a2, nuclear receptor subfamily 4 group A member 2) is needed for the development of ventral midbrain dopaminergic neurons, and has been associated with Parkinson's disease. We used mice where the Nurr1 gene is ablated by tamoxifen treatment selectively in dopaminergic neurons. As a control, we used tamoxifen-treated mice where Nurr1 is not ablated. By laser microdissection of neurons selected by their TH1 (Th1l, TH1-like homolog) gene expression, we selected dopaminergic neurons for RNA extraction and high-throughput mRNA sequencing, in order to identify genes regulated by Nurr1. We found the main functional category of Nurr1-regulated genes are the nuclear-encoded mitochondrial genes. Dopaminergic neurons with or without Nurr1 knocked out. TH-positive neurons were laser capture microdissected from cryostat coronal sections of the midbrain.

2013-01-14 | E-GEOD-42912 | biostudies-arrayexpress

Transcriptome profiles of contrasting potato (Solanum tuberosum L.) genotypes under water stress

Project description:The potato is susceptible to water stress at all stages of development. We examined four clones of tetraploid potato, Cardinal, Desirée, Clone 37 FB and Mije, from the germplasm bank of the National Institute of Agricultural Research (INIA) in Chile. Water stress was applied by suspending irrigation at the beginning of tuberization. Stomatal conductance, tuber and plant fresh and dry weight was used to categorize water stress tolerance. Cardinal had high susceptibility to water stress. Desirée was less suscepetible than Cardinal and had some characteristics of tolerance. Mije had moderate and Clon 37 FB high tolerance. Differential gene expression in leaves from plants with and without water stress were examined using transcriptome sequencing. Water stress susceptible Cardinal had the fewest differentially expressed genes at 101, compared to Desirée at 1867, Clon 37 FB at 1179 and Mije at 1010. Water stress tolerance was associated with up-regulation of expression of transcription factor genes and genes involved in osmolyte and polyamine biosynthesis. Increased expression of genes encoding late embryogenesis abundant (LEA) and dehydrin proteins along with decreased expression of genes involved in nitrate assimilation and amino acid metabolism were found for clones showing water stress tolerance. The results also show that water deficit was associated with reduced biotic stress responses. Additionally, heat shock protein genes were differentially expressed in all clones except for highly susceptible Cardinal. Together the gene expression study demonstrates variation in the molecular pathways and biological processes in response to water stress contributing to tolerance and susceptibility.

2019-12-18 | GSE140083 | GEO

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