Targeted single cell expression profiling identifies integrators of sleep and metabolic state.
Meng-Fu Maxwell Shih1,2,3, Jiwei Zhang2, Elizabeth B Brown2
1Dept of Anesthesiology, Stony Brook School of Medicine, Stony Brook NY, 11794.
Biorxiv : the Preprint Server for Biology
|October 10, 2024
Summary
Fruit flies suppress sleep when starved, relying on specific neurons to signal starvation. This study identified key genes within these neurons that regulate sleep and metabolism during starvation.
Area of Science:
- Neuroscience
- Genetics
- Metabolism
Background:
- Animals adjust sleep based on environmental cues, particularly metabolic signals like food availability.
- Fruit flies (Drosophila melanogaster) reduce sleep when food-deprived, a process mediated by Lateral Horn Leucokinin (LHLK) neurons.
Purpose of the Study:
- To investigate the transcriptional changes in LHLK neurons during starvation.
- To identify novel genes involved in regulating sleep-metabolism interactions at the single-neuron level.
Main Methods:
- Single-cell sequencing (Patch-seq and CEL-Seq) of LHLK neurons from fed and starved fruit flies.
- Differential gene expression analysis to identify starvation-responsive transcripts.
- Gene knockdown experiments to validate the function of identified genes.
Main Results:
- 24 genes, including 12 upregulated and 12 downregulated, were differentially expressed in LHLK neurons upon starvation.
- Gene ontology analysis revealed enrichment of anti-microbial peptides (Attacins) and other cellular function regulators.
- Knockdown of specific genes, including E3 ubiquitin Ligase insomniac, Sodh1, AttacinC, and AttacinB, impaired starvation-induced sleep suppression.
Conclusions:
- This study establishes a method for dissecting neuronal responses to metabolic states.
- Identified key genes, such as insomniac, Sodh1, AttacinC, and AttacinB, play crucial roles in mediating sleep modulation during starvation in fruit flies.
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