Unified Mass Imaging Maps the Lipidome of Vertebrate Development

Halima H. Schede, Leila H. A. Alieh, Laurie A. Rohde, Antonio Herrera, Anjalie Schlaeppi, Guillaume Valentin, Alireza Gargoorimothlag, Albert Dominguez Mantes, Celine Jollivet, Julijana Paz-Montoya, Lucile Capolupo, Irina Khven, Andrew C. Oates, Giovanni D’Angelo, Gioele La Manno

Abstract

The lipidome orchestrates membrane properties, signaling, and metabolism, yet its spatial organization during embryogenesis remains largely uncharted. Here we present uMAIA (unified Mass Imaging Analyzer), an analytical framework for the joint analysis of large mass spectrometry imaging (MSI) datasets. Using uMAIA, we mapped the four-dimensional (4D) distribution of over a hundred lipids at micrometric resolution in Danio rerio (zebrafish) embryos across multiple developmental stages. We discovered metabolic trajectories that unfold in concert with morphogenesis and revealed spatially organized biochemical coordination overlooked by bulk measurements. Lipid mapping revealed unexpected distributions of sphingolipid and triglyceride species, suggesting their involvement in patterning and organ development. Our approach empowers a new generation of whole-organism metabolomic atlases.