Fasting induces metabolic switches and spatial redistributions of lipid processing and neuronal interactions in tanycytes

Maxime Brunner, David Lopez-Rodriguez, Judith Estrada-Meza, Rafik Dali, Antoine Rohrbach, Tamara Deglise, Andrea Messina, Bernard Thorens, Federico Santoni () and Fanny Langlet ()
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Maxime Brunner: Lausanne University Hospital
David Lopez-Rodriguez: University of Lausanne
Judith Estrada-Meza: University of Lausanne
Rafik Dali: University of Lausanne
Antoine Rohrbach: University of Lausanne
Tamara Deglise: University of Lausanne
Andrea Messina: Lausanne University Hospital
Bernard Thorens: University of Lausanne
Federico Santoni: Lausanne University Hospital
Fanny Langlet: University of Lausanne

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract The ependyma lining the third ventricle (3V) in the mediobasal hypothalamus plays a crucial role in energy balance and glucose homeostasis. It is characterized by a high functional heterogeneity and plasticity, but the underlying molecular mechanisms governing its features are not fully understood. Here, 5481 hypothalamic ependymocytes were cataloged using FACS-assisted scRNAseq from fed, 12h-fasted, and 24h-fasted adult male mice. With standard clustering analysis, typical ependymal cells and β2-tanycytes appear sharply defined, but other subpopulations, β1- and α-tanycytes, display fuzzy boundaries with few or no specific markers. Pseudospatial approaches, based on the 3V neuroanatomical distribution, enable the identification of specific versus shared tanycyte markers and subgroup-specific versus general tanycyte functions. We show that fasting dynamically shifts gene expression patterns along the 3V, leading to a spatial redistribution of cell type-specific responses. Altogether, we show that changes in energy status induce metabolic and functional switches in tanycyte subpopulations, providing insights into molecular and functional diversity and plasticity within the tanycyte population.

Date: 2024
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DOI: 10.1038/s41467-024-50913-w

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