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

Dowsett, Georgina K.C. ; Lam, Brian Y.H. ; Tadross, John A. ; Cimino, Irene ; Rimmington, Debra ; Coll, Anthony P. ; Polex-Wolf, Joseph ; Knudsen, Lotte Bjerre ; Pyke, Charles ; Yeo, Giles S.H.

Molecular metabolism (Germany), 2021-11, Vol.53, p.101240-101240, Article 101240 [Periódico revisado por pares]

Germany: Elsevier GmbH

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  • Título:
    A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing
  • Autor: Dowsett, Georgina K.C. ; Lam, Brian Y.H. ; Tadross, John A. ; Cimino, Irene ; Rimmington, Debra ; Coll, Anthony P. ; Polex-Wolf, Joseph ; Knudsen, Lotte Bjerre ; Pyke, Charles ; Yeo, Giles S.H.
  • Assuntos: Animals ; Area postrema ; Area Postrema - metabolism ; Eating ; Fasting ; Feeding Behavior ; Gene expression ; Mice ; Mice, Inbred C57BL ; Neurons - metabolism ; Nucleus tractus solitarius ; Obesity ; Original ; Proprotein Convertase 1 - genetics ; Proprotein Convertase 1 - metabolism ; Proprotein Convertase 2 - genetics ; Proprotein Convertase 2 - metabolism ; Rhombencephalon - metabolism ; Sequence Analysis, RNA ; Solitary Nucleus - metabolism ; Therapeutics
  • É parte de: Molecular metabolism (Germany), 2021-11, Vol.53, p.101240-101240, Article 101240
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: 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. 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. 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. 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. •We provide a survey of 16,034 cells of the murine AP and NTS in the fed and fasted state by single-nucleus RNA sequencing.•8,910 are grouped into 30 neuronal clusters, and 7,124 are non-neuronal such as oligodendrocytes, astrocytes and microglia.•We examine the transcriptomes of populations expressing Glp1r, Gipr, Gfral, Calcr, and Pomc.•The expression profiles for the above populations were not dramatically altered by an overnight fast.•We provide a detailed single-cell level characterisation of AP and NTS cells expressing anti-obesity drug targets.
  • Editor: Germany: Elsevier GmbH
  • Idioma: Inglês
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