Single cell tracing of Pomc neurons reveals recruitment of 'Ghost' subtypes with atypical identity in a mouse model of obesity.

Animals Pro-Opiomelanocortin / metabolism Neurons / metabolism Obesity / metabolism Male Mice Hypothalamus / metabolism Single-Cell Analysis Disease Models, Animal Diet, High-Fat Mice, Inbred C57BL Mice, Transgenic Neurogenesis Mice, Obese

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
24 Apr 2024
Historique:
received: 13 11 2023
accepted: 09 04 2024
medline: 25 4 2024
pubmed: 25 4 2024
entrez: 24 4 2024
Statut: epublish

Résumé

The hypothalamus contains a remarkable diversity of neurons that orchestrate behavioural and metabolic outputs in a highly plastic manner. Neuronal diversity is key to enabling hypothalamic functions and, according to the neuroscience dogma, it is predetermined during embryonic life. Here, by combining lineage tracing of hypothalamic pro-opiomelanocortin (Pomc) neurons with single-cell profiling approaches in adult male mice, we uncovered subpopulations of 'Ghost' neurons endowed with atypical molecular and functional identity. Compared to 'classical' Pomc neurons, Ghost neurons exhibit negligible Pomc expression and are 'invisible' to available neuroanatomical approaches and promoter-based reporter mice for studying Pomc biology. Ghost neuron numbers augment in diet-induced obese mice, independent of neurogenesis or cell death, but weight loss can reverse this shift. Our work challenges the notion of fixed, developmentally programmed neuronal identities in the mature hypothalamus and highlight the ability of specialised neurons to reversibly adapt their functional identity to adult-onset obesogenic stimuli.

Identifiants

DOI: 10.1038/s41467-024-47877-2 PMID: 38658557
pubmed: 38658557
doi: 10.1038/s41467-024-47877-2
pii: 10.1038/s41467-024-47877-2
doi:

Substances chimiques

Pro-Opiomelanocortin 66796-54-1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3443

Subventions

Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-20-CE14-0046

Informations de copyright

© 2024. The Author(s).

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Auteurs

Stéphane Leon (S)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.
ORCID: 0000-0002-2738-2374

Vincent Simon (V)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.
ORCID: 0000-0002-1751-218X

Thomas H Lee (TH)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.

Lukas Steuernagel (L)

Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany.
ORCID: 0000-0003-0043-1436

Samantha Clark (S)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.

Nasim Biglari (N)

Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany.

Thierry Lesté-Lasserre (T)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.

Nathalie Dupuy (N)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.

Astrid Cannich (A)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.

Luigi Bellocchio (L)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.

Philippe Zizzari (P)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.
ORCID: 0000-0001-8838-0762

Camille Allard (C)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.
ORCID: 0000-0002-2198-6011

Delphine Gonzales (D)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.
ORCID: 0000-0002-6307-4280

Yves Le Feuvre (Y)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.

Emeline Lhuillier (E)

University of Toulouse III Paul Sabatier, INSERM, Institut des Maladies Métaboliques et Cardiovasculaires, U1297, 31400, France; GeT-Santé, Plateforme Génome et Transcriptome, GenoToul, Toulouse, France.
ORCID: 0000-0003-2629-7773

Alexandre Brochard (A)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.
ORCID: 0000-0003-0321-7574

Jean Charles Nicolas (JC)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.

Jérémie Teillon (J)

University of Bordeaux, CNRS, INSERM, BIC, US4, UAR 3420, F-33000, Bordeaux, France.

Macha Nikolski (M)

University of Bordeaux, Bordeaux Bioinformatics Center, Bordeaux, France.
University of Bordeaux, CNRS, IBGC UMR 5095, Bordeaux, France.
ORCID: 0000-0001-6059-577X

Giovanni Marsicano (G)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.
ORCID: 0000-0003-3804-1951

Xavier Fioramonti (X)

University of Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France.
ORCID: 0000-0003-1713-4817

Jens C Brüning (JC)

Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany.
Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Cologne, Germany.
Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) University of Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
National Center for Diabetes Research (DZD), Neuherberg, Germany.
ORCID: 0000-0002-6619-0092

Daniela Cota (D)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.
ORCID: 0000-0002-6909-2156

Carmelo Quarta (C)

University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France. carmelo.quarta@inserm.fr.
ORCID: 0000-0002-1352-4239

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Précurseurs de protéines › Pro-opiomélanocortine › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › Cellules › Neurones › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Diencéphale › Hypothalamus › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Analyse sur cellule unique › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › Phénomènes physiologiques › Alimentation et nutrition › Phénomènes physiologiques nutritionnels › Régime alimentaire › Alimentation riche en graisse › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Neurogenèse › Single cell tracing of Pomc neurons reveals...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris obèse › Single cell tracing of Pomc neurons reveals...