Evidence map›Paper›PMID 33962048›Full record

ArticleMolecular metabolism2021

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

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

Open access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
10.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. The critical role of gut-brain signalling in eating behaviour and obesity.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  4. Article
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  9. Cellular coding of ingestion in the caudal brainstem.bioRxiv : the preprint server for biology · 2026
    Article
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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 3 countries.

Georgina K C DowsettMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. Electronic address: Dowsett.gkcd2@cam.ac.uk.
Brian Y H LamMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. Electronic address: Lam.yhbl2@cam.ac.uk.
John A TadrossMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK; Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK. Electronic address: Tadross.jt636@medschl.cam.ac.uk.
Irene CiminoMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. Electronic address: ic326@medschl.cam.ac.uk.
Debra RimmingtonMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. Electronic address: dy222@cam.ac.uk.
Anthony P CollMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. Electronic address: apc36@cam.ac.uk.
Joseph Polex-WolfGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark. Electronic address: jhpw@novonordisk.com.
Lotte Bjerre KnudsenGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark. Electronic address: lbkn@novonordisk.com.
Charles PykeGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark. Electronic address: pyke@novonordisk.com.
Giles S H YeoMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. Electronic address: gshy2@cam.ac.uk.
University of Cambridge · GBNovo Nordisk (Denmark) · DK

Funding

Biotechnology and Biological Sciences Research Council BB/S017593/1Cancer Research UKDepartment of HealthMedical Research Council MC_UU_00014/1Medical Research Council MC_UU_00014/5Wellcome Trust 208363/Z/17/Z
6 · The paper itself

Abstract

objectiveThe 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.

methodsUsing 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.

resultsOf 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.

conclusionWe 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.

Indexed as

EatingFastingAnimalsArea PostremaFeeding BehaviorMiceMice, Inbred C57BLNeuronsProprotein Convertase 1Proprotein Convertase 2RhombencephalonSequence Analysis, RNASolitary NucleusPcsk1 protein, mousePcsk2 protein, mouseProprotein Convertase 1Proprotein Convertase 2Area postremaGene expressionNucleus tractus solitariusObesityTherapeutics

Identifiers

PMID33962048
PMCPMC8170503
OpenAlexW3158537114

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.