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

Stéphane Leon, Vincent Simon, Thomas H. Lee, Lukas Steuernagel, Samantha Clark, Nasim Biglari, Thierry Lesté-Lasserre, Nathalie Dupuy, Astrid Cannich, Luigi Bellocchio, Philippe Zizzari, Camille Allard, Delphine Gonzales, Yves Feuvre, Emeline Lhuillier, Alexandre Brochard, Jean Charles Nicolas, Jérémie Teillon, Macha Nikolski, Giovanni Marsicano, Xavier Fioramonti, Jens C. Brüning, Daniela Cota and Carmelo Quarta ()
Additional contact information
Stéphane Leon: U1215
Vincent Simon: U1215
Thomas H. Lee: U1215
Lukas Steuernagel: Max Planck Institute for Metabolism Research
Samantha Clark: U1215
Nasim Biglari: Max Planck Institute for Metabolism Research
Thierry Lesté-Lasserre: U1215
Nathalie Dupuy: U1215
Astrid Cannich: U1215
Luigi Bellocchio: U1215
Philippe Zizzari: U1215
Camille Allard: U1215
Delphine Gonzales: U1215
Yves Feuvre: U1215
Emeline Lhuillier: GenoToul
Alexandre Brochard: U1215
Jean Charles Nicolas: U1215
Jérémie Teillon: UAR 3420
Macha Nikolski: Bordeaux Bioinformatics Center
Giovanni Marsicano: U1215
Xavier Fioramonti: UMR 1286
Jens C. Brüning: Max Planck Institute for Metabolism Research
Daniela Cota: U1215
Carmelo Quarta: U1215

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract 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.

Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47877-2

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DOI: 10.1038/s41467-024-47877-2

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