[Cellular barcoding and next-generation lineage tracing: concepts and applications]

Lineage tracing is a fundamental technique for dissecting cell fate decisions and development process. With recent advances in high-throughput sequencing and single-cell sequencing technologies, cellular barcoding-based lineage tracing strategies have transitioned from low-throughput labeling methods to high-resolution, multidimensional lineage reconstruction. In this review, we systematically summarize four major barcoding paradigms: viral integration-based random integration barcodes, transposon-based random integration barcodes, recombinase-mediated DNA rearrangement (e.g., Cre-loxP), and CRISPR-Cas9-based mutation recording systems. We describe their principles, representative studies, technical advantages, and limitations. Furthermore, we discuss the core bottlenecks in terms of editing precision, integration of spatiotemporal information, and non-invasive lineage tracing, with a focus on cutting-edge advancements such as prime editing, sequential recording systems, strategies for integrating spatial transcriptomics, and epigenetic tracing. Overall, single-cell lineage tracing is evolving from clonal labeling toward the multi-dimensional integration of lineage, state, and space. In the future, the deep integration of precise gene-editing tools with high-resolution spatial omics technologies is expected to enable dynamic and systematic analysis of cellular fate trajectories, thereby providing critical technical support for research in developmental biology and regenerative medicine.