Dataset Information

A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing.

ABSTRACT:

Objective

The area postrema (AP) and nucleus tractus solitarius (NTS) located in the hindbrain are key nuclei that sense and integrate peripheral nutritional signals and consequently regulate feeding behaviour. While single-cell transcriptomics have been used in mice to reveal the gene expression profile and heterogeneity of key hypothalamic populations, similar in-depth studies have not yet been performed in the hindbrain.

Methods

Using single-nucleus RNA sequencing, we provide a detailed survey of 16,034 cells within the AP and NTS of mice in the fed and fasted states.

Results

Of these, 8,910 were neurons that group into 30 clusters, with 4,289 from mice fed ad libitum and 4,621 from overnight fasted mice. A total of 7,124 nuclei were from non-neuronal cells, including oligodendrocytes, astrocytes, and microglia. Interestingly, we identified that the oligodendrocyte population was particularly transcriptionally sensitive to an overnight fast. The receptors GLP1R, GIPR, GFRAL, and CALCR, which bind GLP1, GIP, GDF15, and amylin, respectively, are all expressed in the hindbrain and are major targets for anti-obesity therapeutics. We characterise the transcriptomes of these four populations and show that their gene expression profiles are not dramatically altered by an overnight fast. Notably, we find that roughly half of cells that express GIPR are oligodendrocytes. Additionally, we profile POMC-expressing neurons within the hindbrain and demonstrate that 84% of POMC neurons express either PCSK1, PSCK2, or both, implying that melanocortin peptides are likely produced by these neurons.

Conclusion

We provide a detailed single-cell level characterisation of AP and NTS cells expressing receptors for key anti-obesity drugs that are either already approved for human use or in clinical trials. This resource will help delineate the mechanisms underlying the effectiveness of these compounds and also prove useful in the continued search for other novel therapeutic targets.

SUBMITTER: Dowsett GKC

PROVIDER: S-EPMC8170503 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Objective: The area postrema (AP) and the nucleus tractus solitaris (NTS), located in the hindbrain, are key nuclei that sense and integrate peripheral nutritional signals and, consequently, regulate feeding behaviour. While single cell transcriptomics have been used in mice to reveal the gene expression profile and heterogeneity of key hypothalamic populations, similar in-depth studies have not yet been performed in the hindbrain. Methods: Using single-nucleus RNA sequencing, we provide a detailed survey of 16,034 cells within the AP and NTS of the mouse, in the fed and fasted state. Results: Of these, 8910 are neurons that group into 30 clusters, with 4289 coming from mice fed ad libitum and 4621 from overnight fasted mice. 7124 nuclei are from non-neuronal cells, including oligodendrocytes, astrocytes and microglia. Interestingly, we identified that the oligodendrocyte population was particularly transcriptionally sensitive to an overnight fast. The receptors GLP1R, GIPR, GFRAL and CALCR, which bind GLP1, GIP, GDF15 and amylin respectively, are all expressed in the hindbrain and are major targets for anti-obesity therapeutics. We characterise the transcriptomes of these four populations and show that their gene expression profiles are not dramatically altered by an overnight fast. Notably, we find that roughly half of cells that express GIPR are oligodendrocytes. Additionally, we profile POMC expressing neurons within the hindbrain and demonstrate that 84% of POMC neurons express either PCSK1, PSCK2 or both, implying that melanocortin peptides are likely produced by these neurons. Conclusion: We provide a detailed single-cell level characterisation of AP and NTS cells expressing receptors for key anti-obesity drugs that are either already approved for human use or are in clinical trials. This resource will help delineate the mechanisms underlying the effectiveness of these compounds, and also prove useful in the continued search for other novel therapeutic targets.