SFEBES2022 Poster Presentations Metabolism, Obesity and Diabetes (96 abstracts)
Single-nucleus RNA sequencing identifies wide-ranging changes in gene expression in mouse nodose ganglia cell populations in response to fasting
Sijing Cheng 1 , Georgina Dowsett 2 , Brian Lam 2 , Mariana Norton 1 , Anna Roberts 1 , Phyllis Phuah 1 , Giles Yeo 2 & Kevin Murphy 1
1Imperial College London, London, United Kingdom; 2University of Cambridge, Cambridge, United Kingdom
Obesity is a leading global health concern. The gut-brain axis is critical to appetite regulation. The vagus nerve represents the major neural pathway between the gastrointestinal tract and the central nervous system, capable of rapidly communicating information about the nutrient content from different regions of the gastrointestinal tract, directly via nutrient receptors expressed on vagal afferents and indirectly by responding to gut hormones and enteric nervous system signalling. The cell bodies of vagal neurons reside in the nodose ganglia, and these cells are known to express various mechano- and chemoreceptors, allowing the body to appropriately regulate processes including gastric motility and appetite. Recent studies have characterised the cell populations comprising the nodose ganglia, but there has been little investigation into how changes in physiological state can alter the gene expression profiles of these cells. Given the importance of vagal signalling in appetite and metabolism, we investigated the response of nodose ganglia cells to fasting. 10X single-nucleus RNA sequencing was performed on left and right murine nodose ganglia extracted from fed and 12-hour fasted mice (n =10, pooled). 1832 nuclei were analysed and identified as belonging to 19 different nodose ganglia cell clusters. There was no difference in cell types between left and right ganglia or fasted and ad libitum status. However, there were wide ranging changes in gene expression across cell types in response to fasting, with neuronal cells showing significant changes in 5008 genes. These included changes in the expression of receptors involved in energy and glucose homeostasis, including the leptin and insulin receptors in specific cell types. These data demonstrate the profound changes in gene expression that occur in nodose ganglia cells in response to altered nutritional status and provide insight into putative targets for the treatment of metabolic disease.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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