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Spatial transcriptomics reveals unique gene expression changes in different brain regions after sleep deprivation
Preprint   Open access

Spatial transcriptomics reveals unique gene expression changes in different brain regions after sleep deprivation

Yann Vanrobaeys, Zeru J Peterson, Emily N Walsh, Snehajyoti Chatterjee, Li-Chun Lin, Lisa C Lyons, Thomas Nickl-Jockschat and Ted Abel
bioRxiv : the preprint server for biology
01/19/2023
DOI: 10.1101/2023.01.18.524406
PMCID: PMC9882298
PMID: 36712009
url
https://doi.org/10.1101/2023.01.18.524406View
Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Sleep deprivation has far-reaching consequences on the brain and behavior, impacting memory, attention, and metabolism. Previous research has focused on gene expression changes in individual brain regions, such as the hippocampus or cortex. Therefore, it is unclear how uniformly or heterogeneously sleep loss affects the brain. Here, we use spatial transcriptomics to define the impact of a brief period of sleep deprivation across the brain. We find that sleep deprivation induced pronounced differences in gene expression across the brain, with the greatest changes in the hippocampus, neocortex, hypothalamus, and thalamus. Both the differentially expressed genes and the direction of regulation differed markedly across regions. Importantly, we developed bioinformatic tools to register tissue sections and gene expression data into a common anatomical space, allowing a brain-wide comparison of gene expression patterns between samples. Our results suggest that distinct molecular mechanisms acting in discrete brain regions underlie the biological effects of sleep deprivation. Spatial transcriptomics using the Visium platform reveals the transcriptional signature across the brain, recapitulating the anatomy of the mouse brainSleep deprivation induces transcriptomic changes unique to each brain regionThe hippocampus is the brain region impacted the most by acute sleep deprivation, with most differentially regulated genes significantly downregulatedThe neocortex exhibits layer-specific changes in gene expression, with most differentially regulated genes significantly upregulatedRegistration of spatial transcriptomic data to a common anatomical reference space (Allen Common Coordinate Framework) allows statistical analysis of gene expression across regions of the brain and for multi-sample analysis.

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