Targeted single cell expression profiling identifies integrators of sleep and metabolic state
Meng-Fu M Shih1, Jiwei Zhang2, Elizabeth B Brown3
1Department of Anesthesiology, Stony Brook School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
G3 (Bethesda, Md.)
|June 13, 2025
Summary
Fruit flies suppress sleep when starved, a process controlled by Lateral Horn Leucokinin (LHLK) neurons. Starvation alters gene expression in these neurons, revealing new regulators of sleep and metabolism.
Area of Science:
- Neuroscience
- Metabolism
- Genetics
Background:
- Animals adjust sleep based on environmental cues, with metabolic status being a key regulator.
- Food availability influences sleep timing and duration, prompting behavioral changes like sleep suppression for foraging.
- In Drosophila melanogaster, starvation-induced sleep suppression is mediated by Lateral Horn Leucokinin (LHLK) neurons.
Purpose of the Study:
- To investigate the transcriptional changes within individual LHLK neurons in response to starvation.
- To identify novel genes and cellular mechanisms involved in regulating sleep-metabolism interactions.
Main Methods:
- Single-cell sequencing (CEL-Seq) of LHLK neurons from fed and starved Drosophila.
- Differential gene expression analysis to identify starvation-responsive transcripts.
- Targeted gene knockdown to functionally validate identified genes in regulating sleep.
Main Results:
- Single-cell sequencing successfully isolated RNA from individual LHLK neurons.
- Starvation led to differential expression of 24 genes in LHLK neurons (12 upregulated, 12 downregulated).
- Key validated genes include Attacins (AttacinC, AttacinB), insomniac (E3 ubiquitin ligase), and Sodh1 (sorbitol dehydrogenase).
Conclusions:
- This study establishes a method for dissecting neuronal transcriptional responses to physiological states.
- Identified genes, including Attacins and insomniac, play crucial roles in starvation-induced sleep suppression.
- Provides a framework for discovering new regulators of sleep-metabolism interactions at the single-neuron level.
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