Bioluminescence-activated proximity labeling for spatial multi-omics

Mapping the spatial organization of proteins and cellular interactions is crucial for understanding their biological functions. Herein, we report a biocompatible, multi-functional luminescence-activated proximity labeling (LAP) strategy for profiling subcellular proteomes and cell-cell interactions in live cells and animals. Our method capitalizes on fusing the photocatalyst miniSOG to NanoLuc luciferase, whose bioluminescence activates miniSOG via a resonance energy transfer mechanism, generating reactive oxygen species in situ to mediate proximity labeling. We achieved local transcriptome profiling by combining LAP with next-generation sequencing.