Cell lineage tracing: Methods, applications, and challenges

Abstract

Cell lineage tracing is a crucial technique for understanding cell fate and lineage relationships, with wide applications in developmental biology, tissue regeneration, and disease progression studies. Over the years, experimental cell lineage tracing methods have advanced from early labeling techniques to modern genetic tools such as CRISPR-Cas9-based barcoding, whereas computational methods have emerged to analyze high-dimensional data from single-cell sequencing and other omics technologies. This paper reviews both experimental and computational methods, highlighting their respective strengths, limitations, and synergies. Experimental techniques focus on labeling and tracking cells, whereas computational approaches reconstruct lineage relationships and model cellular dynamics. Despite significant progress, challenges remain, including issues with accuracy, resolution, multi-omics integration, and scalability. Future directions involve improvements in experimental techniques and the development of computational methods enhanced by advancements in artificial intelligence. These innovations are expected to drive the field forward, offering potential applications in uncovering the mysteries of life.

Keywords: CRISPR‐Cas9; RNA velocity; cell lineage tracing; single‐cell sequencing.