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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 10, 2021 |
| Title |
A survey of the mouse hindbrain in the fed and fasted state using single-nucleus RNA sequencing. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Single-nucleus RNA sequencing data from 6 mice fed ad libitum and 6 mice fasted overnight, aged 6-8 weeks.
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| Contributor(s) |
Dowsett GK, Lam BY, Yeo GS |
| Citation(s) |
33962048 |
| Submission date |
Mar 11, 2021 |
| Last update date |
May 12, 2021 |
| Contact name |
Brian Yee Hong Lam |
| E-mail(s) |
yhbl2@cam.ac.uk
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| Organization name |
University of Cambridge
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| Department |
Metabolic Research Laboratories
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| Street address |
Box 289 Addenbookes Hospital, Hills Road
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0QQ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| GSM5163373 |
Mouse AP/NTS ad libitum fed repitition 1 |
| GSM5163374 |
Mouse AP/NTS ad libitum fed repitition 2 |
| GSM5163375 |
Mouse AP/NTS overnight fasted repitition 1 |
| GSM5163376 |
Mouse AP/NTS overnight fasted repitition 2 |
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| Relations |
| BioProject |
PRJNA713793 |
| SRA |
SRP310271 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE168737_RAW.tar |
62.2 Mb |
(http)(custom) |
TAR (of H5) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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