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

Author

Listed:
  • 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
    CNRS)

  • Giovanni Marsicano

    (U1215)

  • Xavier Fioramonti

    (UMR 1286)

  • Jens C. Brüning

    (Max Planck Institute for Metabolism Research
    University Hospital Cologne
    Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) University of Cologne
    University of Cologne)

  • Daniela Cota

    (U1215)

  • Carmelo Quarta

    (U1215)

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.

Suggested Citation

  • Stéphane Leon & Vincent Simon & Thomas H. Lee & Lukas Steuernagel & Samantha Clark & Nasim Biglari & Thierry Lesté-Lasserre & Nathalie Dupuy & Astrid Cannich & Luigi Bellocchio & Philippe Zizzari & Ca, 2024. "Single cell tracing of Pomc neurons reveals recruitment of ‘Ghost’ subtypes with atypical identity in a mouse model of obesity," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47877-2
    DOI: 10.1038/s41467-024-47877-2
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    References listed on IDEAS

    as
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