Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells

ABSTRACT: Cellular metabolism is important for adult neural stem/progenitor cell (NSPC) behavior. However, its role in the transition from quiescence to proliferation is not fully understood. We here show that the mitochondrial pyruvate carrier (MPC) plays a crucial and unexpected part in this process. MPC transports pyruvate into mitochondria, linking cytosolic glycolysis to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Despite its metabolic key function, the role of MPC in NSPCs has not been addressed. We show that quiescent NSPCs have an active mitochondrial metabolism and express high levels of MPC. Pharmacological MPC inhibition increases aspartate and triggers NSPC activation. Furthermore, genetic Mpc1 ablation in vitro and in vivo also activates NSPCs, which differentiate into mature neurons, leading to overall increased hippocampal neurogenesis in adult and aged mice. These findings highlight the importance of metabolism for NSPC regulation and identify an important pathway through which mitochondrial pyruvate import controls NSPC quiescence and activation.

ORGANISM(S): Mus musculus

PROVIDER: GSE220663 | GEO | 2023/01/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Metabolic control of adult neural stem cell self-renewal by the mitochondrial protease YME1L

Project description:The transition between quiescence and activation in neural stem and progenitor cells (NSPCs) is coupled to reversible changes in energy metabolism with key implications for life-long NSPC self-renewal and neurogenesis. How this metabolic plasticity is ensured between NSPC activity states is unclear. We find that a state-specific rewiring of the mitochondrial proteome by the i-AAA peptidase YME1L is required to preserve NSPC self-renewal. YME1L controls the abundance of numerous mitochondrial substrates in quiescent NSPCs, and its deletion activates a differentiation program characterized by broad metabolic changes causing the irreversible shift away from a fatty acid oxidation-dependent state. Conditional Yme1l deletion in adult NSPCs in vivo results in defective self-renewal and premature differentiation, ultimately leading to NSPC pool depletion. Our results disclose an important role for YME1L in coordinating the switch between metabolic states of NSPCs and suggest that NSPC fate is regulated by compartmentalized changes in protein network dynamics.

2022-02-10 | PXD030995 | Pride

A fatty acid oxidation-dependent metabolic shift regulates adult neural stem cell quiescence

Project description:Adult hippocampal neurogenesis is important for certain forms of cognition and failing neurogenesis has been implicated in neuropsychiatric diseases. The neurogenic capacity of hippocampal neural stem/progenitor cells (NSPCs) depends on a balance between quiescent and proliferative states. However, how this balance is regulated remains poorly understood. Here we show that the rate of fatty acid oxidation (FAO) defines quiescence vs. proliferation in NSPCs. Quiescent NSPCs show high levels of carnitine palmitoyltransferase 1a (Cpt1a)-dependent FAO, which is downregulated in proliferating NSPCs. Pharmacological inhibition and conditional deletion of Cpt1a in vitro and in vivo leads to altered NSPC behavior, showing that Cpt1a-dependent FAO is required for stem cell maintenance and proper neurogenesis. Strikingly, experimental manipulation of malonyl-CoA, the metabolite that regulates levels of FAO, is sufficient to induce exit from quiescence and to enhance NSPC proliferation. Thus, the data presented here identify a shift in FAO metabolism that governs NSPC behavior and suggest an instructive role for fatty acid metabolism in regulating NSPC activity.

2019-11-15 | PXD005598 | Pride

Mitochondrial Pyruvate Carrier 1 (MPC1) enforces T cell homeostasis by enabling pyruvate oxidation in the mitochondria

Project description:The transporter which uptakes pyruvate into the mitochondria during pyruvate oxidation, called the Mitochondrial Pyruvate Carrier (MPC), was only recently identified. While the MPC has been studied in a variety of cell types, including cancer cells and stem cells, very little is known about the importance of MPC in immune cells. Here, we delete MPC from hematopoietic cells and measure its impact on T cell gene expression.

2020-04-27 | GSE122711 | GEO

Metabolic control of adult neural stem cell self-renewal by the mitochondrial protease YME1L

2022-01-19 | GSE193551 | GEO

The mitochondrial pyruvate carrier regulates antitumor function and memory T cell differentiation

Project description:Effector CD8+ T cells engage glycolysis for both lactate fermentation and pyruvate oxidation, the latter requiring the mitochondrial pyruvate carrier (MPC). How mitochondrial pyruvate metabolism impacts T cell function and fate, remains incompletely understood. We found that genetic deletion of MPC drives CD8+ T cell differentiation towards a memory phenotype. Metabolic flexibility induced by MPC inhibition in a nutrient-rich environment allowed for increased acetyl-coenzyme-A production by glutamine and fatty acid oxidation. This correlated with histone acetylation and chromatin accessibility on pro-memory genes. However, in a nutrient-deprived tumor microenvironment, MPC is essential for sustaining lactate oxidation that limits the metabolic suppression of CD8+ T cell anti-tumor function. To optimally translate these findings, we used a small molecule MPC inhibitor to imprint a stable memory phenotype during chimeric antigen receptor (CAR) T manufacturing, and demonstrated that infusing metabolically conditioned MPC WT CAR T cells resulted in superior and long-lasting anti-tumor activity.

2022-04-20 | GSE184718 | GEO

Lipid droplet availability affects neural stem/progenitor cell metabolism and proliferation

Project description:Neural stem/progenitor cells (NSPCs) generate new neurons throughout adulthood. However, the underlying regulatory processes are still not fully understood. Lipid metabolism plays an important role in regulating NSPC activity: build-up of lipids is crucial for NSPC proliferation, whereas break-down of lipids has been shown to regulate NSPC quiescence. Despite their central role for cellular lipid metabolism, the role of lipid droplets (LDs), the lipid storing organelles, in NSPCs remains underexplored. Here we show that LDs are highly abundant in adult mouse NSPCs, and that LD accumulation is significantly altered upon fate changes such as quiescence and differentiation. NSPC proliferation is influenced by the number of LDs, inhibition of LD build-up, breakdown or usage, and the asymmetric inheritance of LDs during mitosis. Furthermore, high LD-containing NSPCs have increased metabolic activity and capacity, but do not suffer from increased oxidative damage. Together, these data indicate an instructive role for LDs in driving NSPC behaviour.

2021-11-10 | GSE187470 | GEO

Mitochondrial Pyruvate Carrier 1 (MPC1) promotes peripheral T cell quiescence through metabolic regulation of thymic development

2019-12-30 | GSE138718 | GEO

RNA sequencing of Mpc1 floxed mouse prostate organoids transduced with RFP control or Cre virus and treated -/+ small molecule MPC inhibitor UK5099

Project description:The goal of this study was to determine how knockout or pharmacological inhibition of the mitochondrial pyruvate carrier (MPC) alters lineage identity in the prostate. We isolated basal cells from Mpc1 floxed mouse prostates and transduced with a control RFP virus or Cre recombinase virus. We then plated into organoid culture and treated with either vehicle or the small molecule MPC inhibitor UK5099 for one week.

2023-09-01 | GSE221022 | GEO

Expression data from proliferating and quiescent adult hippocampal neural stem and progenitor cells

Project description:We have characterized the transcriptome of adult rat hippocampal neural stem and progenitor cell (NSPC) cultures. The NSPCs cultures can be reversibly arrested by the quiescence-promoting signal BMP4. We provide expression data from NSPCs grown as neurospheres for 4 days in vitro in the presence of FGF2 (proliferating NSPCs) or FGF2+BMP4 (quiescent NSPCs) showing that entry into quiescence involves major changes in the transcriptional profile of the cells.

2020-09-29 | GSE158658 | GEO

Mitochondrial Pyruvate Carrier 1 (MPC1) promotes peripheral T cell quiescence through metabolic regulation of thymic development

Project description:Mitochondrial Pyruvate Carrier 1 (MPC1) promotes peripheral T cell quiescence through metabolic regulation of thymic development

| PRJNA576898 | ENA

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