Sleep Loss Amplifies the Neuron-Specific Interleukin-1 Receptor Accessory Protein Oncogenic Roles
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1099654 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To gain molecular insights into the roles of neuron-specific interleukin-1 receptor accessory protein (AcPb)-dependent responses to sleep disruption (SD), we utilized RNA-seq to compare gene expression in the brains of wild-type (WT) and AcPb-/- mice, both with and without SD.
2024-12-18 | GSE263872 | GEO
Project description:Transcriptomic DN3 clock neuron subtypes regulate Drosophila sleep
| PRJNA1155627 | ENA
Project description:Circadian neurons within animal brains orchestrate myriad physiological processes and behaviors, but the contribution of these neurons to the regulation of sleep is not well understood. To address this deficiency, we leveraged single-cell RNA sequencing to generate a new and now comprehensive census of transcriptomic cell types of Drosophila clock neurons. We focused principally on the enigmatic DN3s, which constitute most fly brain clock neurons and were previously almost completely uncharacterized. These DN3s are organized into 12 clusters with unusual gene expression features compared to the more well-studied clock neurons. We further show that previously uncharacterized DN3 subtypes promote sleep through a G protein–coupled receptor, TrissinR. Our findings indicate an intricate regulation of sleep behavior by clock neurons and highlight their remarkable diversity in gene expression and functional properties.
2024-11-20 | GSE276175 | GEO
Project description:Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids.
| PRJNA1061096 | ENA
Project description:The metronome-like circadian regulation of sleep timing must still adapt to an uncertain environment. Recent studies in Drosophila indicate that neuromodulation not only plays a key role in clock neuron synchronization but also affects interactions between the clock network and brain sleep centers. We show here that the targets of neuromodulators, G-Protein Coupled Receptors (GPCRs), are highly enriched in the fly brain circadian clock network. Single cell sequencing indicates that they are not only enriched, but they are also differentially expressed and contribute to clock neuron identity. We generated a comprehensive guide library to mutagenize individual GPCRs in specific neurons and verified the strategy by introducing a targeted sequencing approach. Combined with a behavioral screen, the mutagenesis strategy revealed a novel role of dopamine in sleep regulation by identifying two dopamine receptors and a clock neuron subpopulation that gate the timing of sleep.
2022-05-09 | GSE202407 | GEO
Project description:Orexin/hypocretin receptor type 2 (Ox2R), which is widely expressed in the brain, receives orexin signals and modulates sleep and metabolism. Ox2R selective agonists are currently under clinical trials for narcolepsy treatment. Nevertheless, it remains unclear whether Ox2R exerts an inhibitory effect via Gi proteins in addition to an excitatory effect via Gq proteins. Here, we focused on Ox2R expression and function in MCH neurons, which have opposite roles to orexin neurons in sleep and metabolism regulation. Ox2R-expressing MCH neurons showed heterogeneity of RNA expression, and orexin B application in brain slices induced both excitatory and inhibitory responses in distinct MCH neuron populations. Ox2R inactivation in MCH neurons reduced transitions from NREM to REM sleep and impaired insulin sensitivity with hyperphagia. In conclusion, Ox2R mediates excitatory and inhibitory responses in MCH neuron subpopulations in vivo, which might regulate sleep and metabolism.
2024-11-19 | GSE281229 | GEO
Project description:The non-coding genome is substantially larger than the protein-coding genome, but has been largely unexplored by genetic association studies. Here, we performed region-based rare-variant association analysis of >25,000 variants in untranslated regions of 6,139 amyotrophic lateral sclerosis (ALS) whole-genomes and those of 70,403 non-ALS controls. We identified Interleukin-18 Receptor Accessory Protein (IL18RAP) 3′UTR variants as significantly enriched in non-ALS genomes and associated with five-fold reduced risk of developing ALS, and this was replicated in an independent cohort. These variants in the IL18RAP 3′UTR reduce mRNA stability and the binding of double-stranded RNA-binding proteins. Finally, the variants of IL18RAP 3′UTR confer a survival advantage for motor neurons because they dampen neurotoxicity of human iPSC-derived microglia bearing an ALS-associated expansion in C9orf72, and this depends on NF-κB signaling. This study reveals genetic variants that protect against ALS by reducing neuroinflammation, and emphasizes the importance of non-coding genetic association studies.
2022-02-09 | GSE186757 | GEO
Project description:A crucial step in understanding the sleep-control mechanism is to identify sleep neurons. In principle, a neuron could promote sleep by inhibiting wake-promoting neurons. Using rabies virus (RV)-mediated transsynaptic tracing, we identified several brain regions with GABAergic neurons that broadly inhibit multiple wake-promoting neuronal populations, and the most prominent source of GABAergic inputs was found in a posterior part of the CeA. The CeA is known to contain multiple subtypes of GABAergic neurons with distinct molecular markers, projection targets, and functional properties. Using translating ribosome affinity purification (TRAP) RNA-Seq, we identified molecular markers for the canditate sleep-promoting neurons in CeA.
2020-04-06 | GSE121888 | GEO
Project description:Short sleep duration is associated with adverse metabolic, cardiovascular, and inflammatory effects. Co-twin study methodologies account for familial (e.g., genetics and shared environmental) confounding, allowing assessment of subtle environmental effects, such as the effect of short habitual sleep duration on gene expression. Therefore, we sought to investigate gene expression in monozygotic twins discordant for actigraphically phenotyped habitual sleep duration. Eleven healthy monozygotic twin pairs (82% female; mean age 42.7 years; SD=18.1), selected based on subjective sleep duration discordance, were objectively phenotyped for habitual sleep duration with two-weeks of wrist actigraphy. Peripheral blood leukocyte (PBL) RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. Differential gene expression was determined between paired samples and mapped to functional categories using Gene Ontology. Next, a more comprehensive gene set enrichment analysis was performed based on the entire PBL transcriptome. The mean 24 hour sleep duration of the total sample was 439.2 minutes (SD=46.8 minutes; range 325.4 to 521.6 minutes). Mean within-pair sleep duration difference per 24 hours was 64.4 minutes (SD=21.2; range 45.9 to 114.6 minutes). The twin cohort displayed distinctive pathway enrichment based on sleep duration differences. Short sleep was associated with up-regulation of genes involved in transcription, ribosome, translation and oxidative phosphorylation. Unexpectedly, genes down-regulated in short sleep twins were highly enriched in immuno-inflammatory pathways such interleukin signaling and leukocyte activation, as well as developmental programs, coagulation cascade, and cell adhesion. Objectively assessed habitual sleep duration in monozygotic twin pairs appears to be associated with distinct patterns of differential gene expression and pathway enrichment. By accounting for familial confounding and measuring real life sleep duration, our study shows the transcriptomic effects of short sleep on dysregulated immune response and provides a potential link between sleep deprivation and adverse metabolic, cardiovascular and inflammatory outcomes.
2016-09-09 | GSE80612 | GEO
Project description:Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids [scATAC-seq]
| PRJNA1061108 | ENA