High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer

All cells in an organism come from other cells. Accordingly, biologists have long sought to understand the dynamics of cell fate determination in development and disease. Koblan et al. developed PEtracer, a prime editing–based evolving lineage-tracing system that uses predefined edits to mark cell divisions over diverse spatial and temporal scales. PEtracer jointly profiles cell state and lineage in intact tissue using both single-cell sequencing and high-resolution, multimodal imaging. Using PEtracer in a syngeneic mouse model of cancer metastasis, the authors uncovered how the interplay between cell-intrinsic programs and spatial organization shapes cancer growth in three dimensions, leading to distinct progams of tumor evolution.