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Autonomous rhythmic activity in glioma networks drives brain tumor growth

ABSTRACT: Autonomous rhythmic activity in glioma networks drives brain tumor growth

PROVIDER: PRJNA889854 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21882946_1.fastq.gz	Fastqsanger.gz
	SRR21882946_2.fastq.gz	Fastqsanger.gz
	SRR21882947_1.fastq.gz	Fastqsanger.gz
	SRR21882947_2.fastq.gz	Fastqsanger.gz
	SRR21882948_1.fastq.gz	Fastqsanger.gz

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Autonomous rhythmic activity in glioma networks drives brain tumor growth

Project description:Glioblastoma cell networks harbor a plastic population of highly active glioblastoma cells that display rhythmic Ca2+ oscillations and are particularly connected to others. Targeting the autonomous rhythmic activity of periodic tumor cells by pharmacological interference with the potassium channel KCa3.1 strongly compromised global network communication. This led to a marked reduction of tumor cell viability within the entire network, reduced tumor growth in mice, and prolonged animal survival. The dependency of glioblastoma networks on periodic Ca2+ activity generates a vulnerability that can be exploited for the development of novel therapies, with KCa3.1 inhibiting drugs as one example. To investigate the molecular mechanism of KCa3.1 blockade, we exposed glioblastoma cells to Senicapoc, a selective inhinitor of the KCa3.1 channel, and performed gene expression profiling analysis using data obtained from RNA-Seq.

2022-10-19 | GSE215365 | GEO

Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice

Project description:Virtually every mammalian tissue exhibits rhythmic expression in thousands of genes, which activate tissue-specific processes at appropriate times of the day. Much of this rhythmic expression is thought to be driven cell-autonomously by molecular circadian clocks present throughout the body. However, increasing evidence suggests that systemic signals, and more specifically rhythmic food intake (RFI), can regulate rhythmic gene expression independently of the circadian clock. To determine the relative contribution of cell autonomous clocks versus RFI in the regulation of rhythmic gene expression, we developed a system that allows long-term manipulation of the daily rhythm of food intake in the mouse, and analyzed liver gene expression by RNA-Seq in mice fed ad libitum, only at night, or arrhythmically (mouse eating 1/8th of their daily food intake every 3 hours). We show that 70% of the cycling mouse liver transcriptome loses rhythmicity under arrhythmic feeding. Remarkably, this loss of rhythmic gene expression under arrhythmic feeding is independent of the liver circadian clock, which continues to exhibit normal oscillations in core clock gene expression. Many genes that lose rhythmicity participate in the regulation of metabolic processes such as lipogenesis and glycogenesis, likely contributing to an increased sensitivity to insulin that was observed in arrhythmically-fed mice. We also show that night-restricted feeding significantly increases the number of rhythmically expressed genes as well as the amplitude of the rhythms. Together, these results indicate that metabolic transcription factors control a large fraction of the rhythmic mouse liver transcriptome, and demonstrate that systemic signals driven by rhythmic food intake play a more important role than the cell-autonomous circadian clock in driving rhythms in liver gene expression and metabolic functions.

2019-04-25 | GSE118967 | GEO

Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice

Project description:Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice

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Rhythmic transcription drives mRNA level oscillations during C. elegans development

Project description:Rhythmic transcription drives mRNA level oscillations during C. elegans development

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Remote neuronal activity drives glioma progression via Sema4F

Project description:Remote neuronal activity drives glioma progression via Sema4F

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Rhythmic transcription drives mRNA level oscillations during C. elegans development [ChIP-Seq]

Project description:Rhythmic transcription drives mRNA level oscillations during C. elegans development [ChIP-Seq]

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Rhythmic transcription drives mRNA level oscillations during C. elegans development [RNA-Seq]

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Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism

Project description:Chronic inflammation underpins many human diseases. The morbidity and mortality of chronic inflammation is often mediated through metabolic dysfunction. Inflammatory and metabolic processes vary through circadian time, suggesting an important temporal crosstalk between these systems. Using an established mouse model of rheumatoid arthritis, here we show thatchronic inflammatory arthritis results in rhythmic joint inflammation and drives major changes in muscle and liver energy metabolism and rhythmic gene expression. Transcriptional and phosphoproteomic analyses reveal alteration in lipid metabolism and mitochondrial function associated with increased EGFR-JAK11 STAT3 signalling. Metabolomic analyses confirmed rhythmic metabolic rewiring with impaired β-oxidation and lipid handling, and revealed a pronounced shunt towards sphingolipid and ceramide accumulation. The arthritis-related production of ceramides was most pronounced during the day, the time of peak inflammation and increased reliance on fatty acid oxidation. Thus, our data demonstrate that localised joint inflammation drives a time-of-day dependent build-up of bioactive lipid species driven by rhythmic inflammation and altered EGFR-STAT signalling.

2022-05-08 | PXD032723 | Pride

NF1 mutation drives neuronal activity-dependent optic glioma initiation

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Coordination of rhythmic RNA synthesis and degradation orchestrates 24- and 12-h RNA expression patterns in mouse fibroblasts

Project description:Circadian RNA expression is essential to ultimately regulate a plethora of downstream rhythmic biochemical, physiological, and behavioral processes. Both transcriptional and post transcriptional mechanisms are considered important to drive rhythmic RNA expression, however, the extent to which each regulatory process contributes to the rhythmic RNA expression remains controversial. To systematically address this, we monitored RNA dynamics using metabolic RNA labeling technology during a circadian cycle in mouse fibroblasts. We find that rhythmic RNA synthesis is the primary contributor of 24 hr RNA rhythms, while rhythmic degradation is more important for 12 hr RNA rhythms. These rhythms were predominantly regulated by Bmal1 and/or the core clock mechanism, and interplay between rhythmic synthesis and degradation has a significant impact in shaping rhythmic RNA expression patterns. Interestingly, core clock RNAs are regulated by multiple rhythmic processes and have the highest amplitude of synthesis and degradation, presumably critical to sustain robust rhythmicity of cell-autonomous circadian rhythms. Our study yields invaluable insights into the temporal dynamics of both 24 hr and 12 hr RNA rhythms in mouse fibroblasts.

2024-01-22 | GSE253826 | GEO

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