Spatial membrane lipid remodeling encodes epithelial lineage and state in human colon cancer

While transcriptomic spatial approaches have advanced rapidly, the spatial organization and functional relevance of tumor lipid metabolism remain poorly understood. Here, we present an integrative spatial multi-omic strategy that anchors high-resolution lipid imaging to transcriptome-defined cellular states.

Applying this approach to human primary and metastatic colon cancer specimens, we jointly profiled spatial lipid distributions and gene expression across tumor epithelial compartments. This approach revealed specific, spatially restricted epithelial lipid phenotypes defined by membrane phospholipid composition. These lipid phenotypes were tightly associated with transcriptional programs reflecting epithelial lineage, differentiation state, and proliferative activity.