Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1246949 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32992975_1.fastq.gz | Fastqsanger.gz | |||
| SRR32992975_2.fastq.gz | Fastqsanger.gz | |||
| SRR32992976_1.fastq.gz | Fastqsanger.gz | |||
| SRR32992976_2.fastq.gz | Fastqsanger.gz | |||
| SRR32992977_1.fastq.gz | Fastqsanger.gz |
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Project description:Metabolic licensing of quiescent glioblastoma activation and immune evasion via astrocyte-mitochondria shuttle
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Project description:Metabolic licensing of quiescent glioblastoma activation and immune evasion via astrocyte-mitochondria shuttle [RNA-Seq]
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Project description:The reaction of quiescent tumor cell subpopulations at the invasive margin of glioblastoma (GBM) might be cleared by immune surveillance toward death or expand through immune escape, which can drive therapeutic resistance, tumor dissemination, and recurrence through phenotypic plasticity. However, the process and mechanisms underlying their activation remain largely unclear. This study revealed that astrocytes awaken quiescent GBM cells to cycling and immune-evasive phenotypes. Astrocytic mitochondria are indispensable in regulating the phenotypic changes. Specifically, the SHMT2 enzyme in astrocytic mitochondria catalyzes one-carbon metabolic products, which significantly promote synthetic metabolic activation and reactivation of quiescent GBM cells to immune evasion through intercellular mitochondrial transfer. Tumor cells that acquire astrocytic mitochondria enhanced one-carbon metabolism drives global hyperactive anabolic metabolism through YTHDC1-mediated transcriptional pause release of ribosomal and focal adhesion signaling genes, supporting rapid proliferation and conferring a potent immune-evasive phenotype. Therapeutically, pharmacologic or genetic inhibiting the astrocytic SHMT2 or blocking mitochondrial transfer markedly suppressed quiescent GBM cell activation and tumor progression. These findings elucidate a novel mechanism by which astrocytes in the tumor microenvironment drive GBM malignancy through metabolic symbiosis.
2026-01-31 | GSE316867 | GEO
Project description:The reaction of quiescent tumor cell subpopulations at the invasive margin of glioblastoma (GBM) might be cleared by immune surveillance toward death or expand through immune escape, which can drive therapeutic resistance, tumor dissemination, and recurrence through phenotypic plasticity. However, the process and mechanisms underlying their activation remain largely unclear. This study revealed that astrocytes awaken quiescent GBM cells to cycling and immune-evasive phenotypes. Astrocytic mitochondria are indispensable in regulating the phenotypic changes. Specifically, the SHMT2 enzyme in astrocytic mitochondria catalyzes one-carbon metabolic products, which significantly promote synthetic metabolic activation and reactivation of quiescent GBM cells to immune evasion through intercellular mitochondrial transfer. Tumor cells that acquire astrocytic mitochondria enhanced one-carbon metabolism drives global hyperactive anabolic metabolism through YTHDC1-mediated transcriptional pause release of ribosomal and focal adhesion signaling genes, supporting rapid proliferation and conferring a potent immune-evasive phenotype. Therapeutically, pharmacologic or genetic inhibiting the astrocytic SHMT2 or blocking mitochondrial transfer markedly suppressed quiescent GBM cell activation and tumor progression. These findings elucidate a novel mechanism by which astrocytes in the tumor microenvironment drive GBM malignancy through metabolic symbiosis.
2025-04-30 | GSE294545 | GEO
Project description:CHMP2B mutant astrocytes revealed an accumulation of autophagosomes, which trigger the observed astrocyte reactivity leading to increased cytokine release, altered mitochondria dynamics and metabolic changes.
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Project description:Quiescence is a reversible cell-cycle arrest used by Cancer Stem Cells (CSCs) to evade killing following conventional therapies. Quiescent CSCs are therefore one of the main cause of cancer recurrence. In glioblastoma, the most common and aggressive primary brain tumors, the quiescent glioblastoma stem-like cells (GSCs) are localized in hypoxic and acidic microenvironments and microenvironmental changes can control cell cycle re-entering of the GSCs. Here, we show that proliferating GSCs isolated from patients can be induced and maintained in a quiescent state by lowering the extracellular pH. Through RNA-seq analysis we characterized the RNA signatures of quiescent versus proliferating GSCs. We identified genes involved in the control of Ca2+ signaling and differentially expressed between the two states. Using the bioluminescent Ca2+ reporter EGFP-aequorin targeted to the mitochondria or the cytosol we explored the changes in Ca2+ homeostasis occurring during the switch from proliferation to quiescence. This remodeling is controlled through store-operated channels (SOCs). SOCs play a causal role since the inhibition of the Ca2+ influx through SOC drives proliferating GSCs to quiescence. We showed that the switch to quiescence is characterized by both an increased capacity of GSCs’ mitochondria to capture Ca2+ and a dramatic and reversible change of mitochondrial morphology from a tubular to a donut shape. Our data suggest that the remodeling of the Ca2+ homeostasis and the reshaping of mitochondria during the transition from proliferation to quiescence constitute a protective mechanism that favors cancer stem-like cells’ survival and their aggressiveness in glioblastoma.
2018-05-31 | GSE93991 | GEO
Project description:Bulk cancer cell populations are known to display distinct metabolic properties compared to their normal counterparts. However, relatively little is known about heterogeneity of metabolic properties within tumors. In this study we show that, analogous to some normal stem cells, breast tumor initiating cells (TICs, also called cancer stem cells) have distinct metabolic properties compared to non-tumorigenic cancer cells (NTCs). Transcriptome profiling using RNA-Seq revealed TICs under-express genes involved in mitochondrial oxidative phosphorylation and although TICs are relatively quiescent, they preferentially perform glycolysis over oxidative phosphorylation compared to NTCs. TICs contain fewer mitochondria and display lower expression and activity of pyruvate dehydrogenase (Pdh), a key regulator of oxidative phosphorylation. Metabolic reprogramming of TICs by pharmacologic activation of Pdh preferentially eliminates TICs in vitro and in vivo. Our findings reveal unique metabolic properties of TICs and indicate that metabolic reprogramming represents a promising strategy for targeting these cells. Examination transcriptome profiles for breast tumor initiating cells (TICs) and non-tumorigenic cells (NTCs)
2014-07-31 | E-GEOD-41286 | biostudies-arrayexpress
Project description:Lactate is the most abundant circulating metabolic intermediate in mammals and an important energy source for many organs. To use lactate as a fuel, it must be oxidized to pyruvate for entry into the TCA cycle. It is usually described that this reaction occurs in the cytosol and requires the mitochondrial pyruvate carrier (MPC) for pyruvate transport into the mitochondria. Here, using 13C stable isotope tracing, we report that lactate can be oxidized in the heart tissue of mice even when the MPC is genetically deleted. MPC-independent lactate import and oxidation within mitochondria is dependent upon the monocarboxylate transporter 1 (MCT1/ Slc16a1). Mitochondria isolated from Mct1iCKO hearts have impaired respiration on lactate but not pyruvate. Lactate import coupled to mitochondrial lactate dehydrogenase activity functions as an electron shuttle which can produce NADH sufficient for respiration even when the TCA cycle is blocked. Cardiac-specific loss of MCT1 leads to rapid decompensation into heart failure with reduced ejection fraction in response to diverse cardiac injuries. Thus, we identify a new mitochondrial electron shuttle that enables the oxidation of lactate and is required to support cardiac energetics under stress conditions.
2024-11-22 | GSE276036 | GEO
Project description:Mitochondrial functions are largely performed by proteins imported from cytosol. Impaired protein import in mitochondria affects the maintenance of intra-mitochondrial anabolic and energy metabolic pathways. It leads to cytosolic accumulation of mistargeted proteins and activation of cellular stress responses. To explore the communication between these mechanism in mammalian system, we targeted the co-chaperone of mitochondrial Hsp70, a GrpE Like protein 1 (Grpel1), in mice. We show that loss of protein import into mitochondrial matrix results in mitochondrial dysfunction, which triggers stress responses. The total shut down of mtHSP70 function by overall knockout of Grpel1 resulted in early embryonic lethality, and tamoxifen-induced skeletal muscle-specific knockout of Grpel1 caused rapid muscular atrophy. We show here, with transcriptomics analysis, that protein-import failure in mitochondria increased cellular proteotoxic stress due to mitochondrial dysfunction. As a control mechanism, it triggered adaptive stress responses, including unfolded protein responses and integrated stress responses. Metabolic profiling of skeletal muscle-specific knockout mice revealed amino acid and TCA cycle intermediates shuttle between serum and muscle.
2022-10-04 | GSE198540 | GEO
Project description:MartínJiménez2017 - Genome-scale reconstruction of the human astrocyte metabolic network
This model is described in the article:
Genome-Scale Reconstruction
of the Human Astrocyte Metabolic Network.
Martín-Jiménez CA,
Salazar-Barreto D, Barreto GE, González J.
Front Aging Neurosci 2017; 9: 23
Abstract:
Astrocytes are the most abundant cells of the central
nervous system; they have a predominant role in maintaining
brain metabolism. In this sense, abnormal metabolic states have
been found in different neuropathological diseases.
Determination of metabolic states of astrocytes is difficult to
model using current experimental approaches given the high
number of reactions and metabolites present. Thus, genome-scale
metabolic networks derived from transcriptomic data can be used
as a framework to elucidate how astrocytes modulate human brain
metabolic states during normal conditions and in
neurodegenerative diseases. We performed a Genome-Scale
Reconstruction of the Human Astrocyte Metabolic Network with
the purpose of elucidating a significant portion of the
metabolic map of the astrocyte. This is the first global
high-quality, manually curated metabolic reconstruction network
of a human astrocyte. It includes 5,007 metabolites and 5,659
reactions distributed among 8 cell compartments,
(extracellular, cytoplasm, mitochondria, endoplasmic reticle,
Golgi apparatus, lysosome, peroxisome and nucleus). Using the
reconstructed network, the metabolic capabilities of human
astrocytes were calculated and compared both in normal and
ischemic conditions. We identified reactions activated in these
two states, which can be useful for understanding the
astrocytic pathways that are affected during brain disease.
Additionally, we also showed that the obtained flux
distributions in the model, are in accordance with
literature-based findings. Up to date, this is the most
complete representation of the human astrocyte in terms of
inclusion of genes, proteins, reactions and metabolic pathways,
being a useful guide for in-silico analysis of several
metabolic behaviors of the astrocyte during normal and
pathologic states.
This model is hosted on
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MODEL1608180000.
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2017-05-18 | MODEL1608180000 | BioModels