Nature Communications (Apr 2024)

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 Le Feuvre,
  • Emeline Lhuillier,
  • Alexandre Brochard,
  • Jean Charles Nicolas,
  • Jérémie Teillon,
  • Macha Nikolski,
  • Giovanni Marsicano,
  • Xavier Fioramonti,
  • Jens C. Brüning,
  • Daniela Cota,
  • Carmelo Quarta

DOI
https://doi.org/10.1038/s41467-024-47877-2
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 14

Abstract

Read online

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.