Unified mass imaging maps the lipidome of vertebrate development
Embryo development entails the formation of anatomical structures with distinct biochemical compositions. Compared with the wealth of knowledge on gene regulation, our understanding of metabolic programs operating during embryogenesis is limited. Mass spectrometry imaging (MSI) has the potential to map the distribution of metabolites across embryo development. Here we established uMAIA, an analytical framework for the joint analysis of large MSI datasets, which enables the construction of multidimensional metabolomic atlases. Employing this framework, we mapped the four-dimensional (4D) distribution of over a hundred lipids at micrometric resolution in Danio rerio embryos. We discovered metabolic trajectories that unfold in concert with morphogenesis and revealed spatially organized biochemical coordination overlooked by bulk measurements. Interestingly, lipid mapping revealed unexpected distributions of sphingolipid and triglyceride species, suggesting their involvement in pattern establishment and organ development. Our approach empowers a new generation of whole-organism metabolomic atlases and enables the discovery of spatially organized metabolic circuits.
Authors
- Leila Haj Abdullah Alieh (ORCID: https://orcid.org/0000-0001-5706-2606)
- Gioele La Manno (ORCID: https://orcid.org/0000-0003-1428-8757)
- Laura Capolupo (ORCID: https://orcid.org/0000-0003-1254-5019)
- Anjalie Schlaeppi (ORCID: https://orcid.org/0000-0001-8719-0166)
- Jonathan Paz Montoya (ORCID: https://orcid.org/0000-0001-6256-6200)
- Giovanni D’Angelo (ORCID: https://orcid.org/0000-0002-0734-4127)
- Albert Dominguez Mantes (ORCID: https://orcid.org/0000-0002-6224-0750)
- Guillaume Valentin (ORCID: https://orcid.org/0000-0003-4596-6282)
- Chloé Jollivet
- Laurel A. Rohde (ORCID: https://orcid.org/0000-0002-4329-9116)
- Andrew C. Oates (ORCID: https://orcid.org/0000-0002-3015-3978)
- Antonio Herrera (ORCID: https://orcid.org/0000-0002-6248-1001)
- Halima Hannah Schede (ORCID: https://orcid.org/0009-0004-7026-1676)
- Irina M. Khven (ORCID: https://orcid.org/0000-0002-8813-0576)
- Alireza Gargoori Motlagh
Institutions
- École Polytechnique Fédérale de Lausanne (CH)
- Friedrich Miescher Institute (CH)
Publication Details
- Journal
- Nature Methods
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1038/s41592-025-02771-7
- Citations
- 5
- Primary Topic
- Metabolomics and Mass Spectrometry Studies
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- Stiftelsen Kristian Gerhard Jebsen
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Staatssekretariat für Bildung, Forschung und Innovation