Using a novel genetic editing system termed intMEMOIR, researchers reveal the cell lineage histories of individual cells within their native tissue context, according to a new study. The new approach provides a powerful new tool for recording cell lineage in diverse cellular systems. During multicellular development, a cell's spatial position and lineage play important roles in cell fate determination. The ability to visualize lineage relationships directly within their native tissues can provide valuable insight into the factors that affect development and disease. This promise has spurred the development of several engineered cell lineage recording systems. However, many of the current techniques used to trace cell lineage require sequencing, which disrupts spatial organization, or require methods that prevent extended recording and germline transmission. Here, Ke-Huan Chow and colleagues present intMEMOIR, a broadly useful, digital lineage recording system that allows engineered cells to record lineage in a format that can be read out in situ. IntMEMOIR uses an integrase-based synthetic barcode system to perform irreversible nucleotide edits to targeted regions of a cell's genetic code. Various combinations of alterations can be read across a population of cells using single-molecule fluorescence in situ hybridization, allowing for the simultaneous analysis of a cell's lineage and transcriptional state within their native tissue. Chow et al. demonstrate the novel approach by reconstructing lineage histories in mouse embryonic stem cells. What's more, the authors use intMEMOIR to link cell lineage, cell fate and spatial structure in the fruit fly brain.