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

Autor: Leon S; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Simon V; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Lee TH; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Steuernagel L; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany., Clark S; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Biglari N; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany., Lesté-Lasserre T; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Dupuy N; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Cannich A; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Bellocchio L; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Zizzari P; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Allard C; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Gonzales D; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Le Feuvre Y; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., 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., Brochard A; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Nicolas JC; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Teillon J; University of Bordeaux, CNRS, INSERM, BIC, US4, UAR 3420, F-33000, Bordeaux, France., Nikolski M; University of Bordeaux, Bordeaux Bioinformatics Center, Bordeaux, France.; University of Bordeaux, CNRS, IBGC UMR 5095, Bordeaux, France., Marsicano G; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Fioramonti X; University of Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France., 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., Cota D; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France., Quarta C; University of Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France. carmelo.quarta@inserm.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 24; Vol. 15 (1), pp. 3443. Date of Electronic Publication: 2024 Apr 24.
DOI: 10.1038/s41467-024-47877-2
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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