lineagetracing

Lineage tracing is a set of experimental and computational approaches used to determine the developmental relationships among cells by recording the progeny of individual cells over time. By following how cells divide and differentiate, researchers aim to reconstruct lineage trees that describe tissue formation, stem cell dynamics, and cellular diversification during development, regeneration, and disease. The techniques may be applied in embryos, organoids, and grown tissues.

Traditional genetic lineage tracing relies on heritable, inducible genetic marks. Recombinase systems such as Cre-loxP or Flp-FRT activate reporter genes or barcodes in selected cells, enabling their descendants to be identified later. More recent strategies use DNA barcodes or CRISPR-based approaches (for example, GESTALT, Scartrace) to generate evolving lineages that can be read out by single-cell sequencing. Natural mutations also serve as clonal markers in some contexts.

Lineage tracing supports studies in developmental biology, stem cell research, neurology, immunology, and cancer. It helps map tissue hierarchies, reveal regenerative potential, and illuminate how genetic or environmental perturbations alter cell fate. Data are typically analyzed by reconstructing lineage trees from barcode patterns or mutational records, using phylogenetic or computational graph methods.

Limitations include technical challenges in labeling efficiency, potential perturbation of normal biology, limited temporal resolution, and biases in barcode representation or recombination. In humans, ethical and practical constraints often require indirect or retrospective approaches. Ongoing developments seek to improve resolution, scalability, and the integration of spatial information with lineage data.