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Peer-reviewedCC BYNature

The lipidomic architecture of the mouse brain

  • Luca Fusar Bassini1
  • Halima Hannah Schede2,1,3
  • Laura Capolupo4,3
  • Leila Haj Abdullah Alieh1,3
  • Irmak Kaysudu3
  • Francesca Venturi1,5
  • Hannah Hochgerner6
  • Alessandro Valente1
  • Colas Droin7,1,3
  • Daniel Trejo Banos8
  • Irina M. Khven1
  • Jean Andrea Maillat3
10 more authors
  • Anne‐Laure Mahul‐Mellier3
  • Antonino Asaro3
  • Doğukan Hazar Ülgen9
  • Pavel Barahtjan3
  • Ece Z. Asirim10,3
  • Anita Nasrallah3,11
  • Carmen Sandi9
  • Ekaterina Krymova8
  • Giovanni D’Angelo3
  • Gioele La Manno12
12 affiliations
  1. 1Laboratory of Brain Development and Biological Data Science, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
  2. 2Implexis, London, UK
  3. 3Lipid Cell Biology Laboratory, Institute of Bioengineering and Global Health Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
  4. 4Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland
  5. 5Laboratory of Computational, Quantitative and Synthetic Biology - Sorbonne University, Paris, France
  6. 6The Laboratory of Single Cell Molecular Neurobiology, Technion, Haifa, Israel
  7. 7Hydroclimat, Aubagne, France
  8. 8Swiss Data Science Center, Zurich, Switzerland
  9. 9Laboratory of Behavioral Genetics, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
  10. 10Centre for Artificial Intelligence, ZHAW School of Engineering, Winterthur, Switzerland
  11. 11UCB Farchim, Bulle, Switzerland
  12. 12Laboratory of Brain Development and Biological Data Science, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. [email protected]
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Abstract

Lipids are fundamental components of the brain, crucial for synaptic transmission and signal propagation. Altered brain lipid composition is associated with common and rare neuropathologies, yet the spatial organization of the mammalian brain lipidome remains insufficiently characterized compared with other modalities 1–6 . Here we mapped the membrane-lipid architecture of the adult mouse brain at micrometric scale, across sexes and during pregnancy. This lipid brain atlas reveals that lipids describe a fine-grained biochemical structure that aligns with functional anatomy. Membrane-lipid spatial heterogeneity clusters into territories, which we termed ‘lipizones’. Lipizones partially mirror cell-type territories, but also capture distal axon terminals. Through lipizones, we (1) reveal the organizing principles of the grey matter lipidome, related to connectivity and cytoarchitecture; (2) discover a new axis of oligodendrocyte heterogeneity in the white matter; and (3) find biochemical zonation in the choroid plexus and in the ventricular walls. We show that this lipidomic architecture can adapt to changing physiological needs. In the brain of pregnant female mice, the white matter is metabolically activated and the cortex undergoes a lipizone-specific remodelling that is particularly pronounced in layer 4. These results are a foundational resource ( https://lbae-v2.epfl.ch/ ) poised to reshape the understanding of lipids in brain development, physiology and pathology.

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Cite

BibTeXRIS
BibTeX
@article{bassini2026lipidomic,
  title = {{The lipidomic architecture of the mouse brain}},
  author = {Luca Fusar Bassini and Halima Hannah Schede and Laura Capolupo and Leila Haj Abdullah Alieh and Irmak Kaysudu and Francesca Venturi and Hannah Hochgerner and Alessandro Valente and Colas Droin and Daniel Trejo Banos and Irina M. Khven and Jean Andrea Maillat and Anne‐Laure Mahul‐Mellier and Antonino Asaro and Doğukan Hazar Ülgen and Pavel Barahtjan and Ece Z. Asirim and Anita Nasrallah and Carmen Sandi and Ekaterina Krymova and Giovanni D’Angelo and Gioele La Manno},
  journal = {Nature},
  year = {2026},
  month = sep,
  doi = {10.1038/s41586-026-11050-0},
  url = {https://doi.org/10.1038/s41586-026-11050-0},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - The lipidomic architecture of the mouse brain
AU  - Luca Fusar Bassini
AU  - Halima Hannah Schede
AU  - Laura Capolupo
AU  - Leila Haj Abdullah Alieh
AU  - Irmak Kaysudu
AU  - Francesca Venturi
AU  - Hannah Hochgerner
AU  - Alessandro Valente
AU  - Colas Droin
AU  - Daniel Trejo Banos
AU  - Irina M. Khven
AU  - Jean Andrea Maillat
AU  - Anne‐Laure Mahul‐Mellier
AU  - Antonino Asaro
AU  - Doğukan Hazar Ülgen
AU  - Pavel Barahtjan
AU  - Ece Z. Asirim
AU  - Anita Nasrallah
AU  - Carmen Sandi
AU  - Ekaterina Krymova
AU  - Giovanni D’Angelo
AU  - Gioele La Manno
PY  - 2026
DA  - 2026/09/23
JO  - Nature
DO  - 10.1038/s41586-026-11050-0
UR  - https://doi.org/10.1038/s41586-026-11050-0
AB  - Lipids are fundamental components of the brain, crucial for synaptic transmission and signal propagation. Altered brain lipid composition is associated with common and rare neuropathologies, yet the spatial organization of the mammalian brain lipidome remains insufficiently characterized compared with other modalities 1–6 . Here we mapped the membrane-lipid architecture of the adult mouse brain at micrometric scale, across sexes and during pregnancy. This lipid brain atlas reveals that lipids describe a fine-grained biochemical structure that aligns with functional anatomy. Membrane-lipid spatial heterogeneity clusters into territories, which we termed ‘lipizones’. Lipizones partially mirror cell-type territories, but also capture distal axon terminals. Through lipizones, we (1) reveal the organizing principles of the grey matter lipidome, related to connectivity and cytoarchitecture; (2) discover a new axis of oligodendrocyte heterogeneity in the white matter; and (3) find biochemical zonation in the choroid plexus and in the ventricular walls. We show that this lipidomic architecture can adapt to changing physiological needs. In the brain of pregnant female mice, the white matter is metabolically activated and the cortex undergoes a lipizone-specific remodelling that is particularly pronounced in layer 4. These results are a foundational resource ( https://lbae-v2.epfl.ch/ ) poised to reshape the understanding of lipids in brain development, physiology and pathology.
SN  - 0028-0836
SN  - 1476-4687
ER  -