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Title Multi-generational mRNA sequence data of pooled Drosophila melanogaster male and female flies from populations selected for long or short night sleep

ABSTRACT: Our objective was to determine whether gene expression in Drosophila melanogaster selectively bred for long or short night sleep duration changes detectably across generations. To meet this objective, we performed transcriptional profiling of ten pooled whole adult individuals from four selected populations and two control populations across 13 generations. We quantified differential expression among selection scheme (long sleep, short sleep, or unselected control), generation (generation 0; then generations 2-13), and sex for each gene.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE202600 | GEO | 2023/07/29

REPOSITORIES: GEO

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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.

Project description:Sleep insufficiency is associated with various disorders (cardiovascular disease, neurodegenerative diseases, immunological disorders.) but the molecular bases for these associations are largely unknown. We used multiple omics techniques to examine changes in the blood of healthy male and female adults voluntarily subjected to 24 h of sleep deprivation followed by up to one day of recovery with normal sleep routines. Thirty-two (14 males, 18 females) healthy adults 22-27 years old donated fasting blood samples prior to (Day 1) and following (Days 2 and 3) a 24-hour period of sleep deprivation. Blood samples were subjected to cell, biochemical, transcriptomic, proteomic and metabolomic analyses. Multi-omics integration analysis showed that sleep deprivation caused marked molecular changes (46.4% transcript genes, 59.3% proteins and 55.6% metabolites) that had not been restored by Day 2. Transient sleep deprivation had the greatest impact on the immune system and, in particular, on neutrophil-mediated immune processes. Correlation analysis with neutrophils suggested the plasma level of superoxidase dismustase-1 (SOD1) and the primary blood mononuclear cell transcriptional profile of the S100A8 gene could be used as biomarkers reflecting the sleep deprivation-associated disordered immunological state. An increased number of immune cells (leukocytes, neutrophils, monocytes, eosinophils, CD4+T), inflammatory factors (TNF-α, INF-γ, Il-6, IL-10, IL-12) and c-reactive protein in blood plasma further demonstrated the dysregulation of the immune system associated with short-term sleep deprivation. Other important findings associated with sleep deprivation included a significant decrease in the plasma melatonin level and an enrichment of molecules in signaling pathways associated with brain disorders, including schizophrenia and neurodegenerative diseases. Taken in concert, these points suggest that disrupted sleep, such as may occur in shift work, perturbs immunological status and may increase the risk for brain disorders in later life.

Dataset Information

Title Multi-generational mRNA sequence data of pooled Drosophila melanogaster male and female flies from populations selected for long or short night sleep

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