Regenerative MedicineLineage Tracing Reaches a New Era With Barcodes, Genetics, and Natural Variants
Understanding how cells make fate decisions — whether to become a heart cell, a neuron, or a cancer cell — is fundamental to regenerative medicine and longevity science. This review from Cell Stem Cell synthesizes the three major strategies researchers now use to track cell lineages: genetic markers that prospectively label cells, synthetic DNA barcodes that enable high-throughput mapping, and naturally occurring genetic variants that allow retrospective tracing. The authors explain how these methods integrate with cutting-edge tools like single-cell sequencing, spatial profiling, and multi-omics. They also cover computational approaches used to decode lineage data. The review serves as both a methodology guide and a forward-looking roadmap for translating clonal analysis into clinical applications, including potential diagnostics and therapies in cancer, tissue regeneration, and stem cell medicine.