Connecting past and present: single-cell lineage tracing

Central to the core principle of cell theory, depicting cells’ history, state and fate is a fundamental goal in modern biology. By leveraging clonal analysis and single-cell RNA-seq technologies, single-cell lineage tracing provides new opportunities to interrogate both cell states and lineage histories. During the past few years, many strategies to achieve lineage tracing at single-cell resolution have been developed, and three of them (integration barcodes, polylox barcodes, and CRISPR barcodes) are noteworthy as they are amenable in experimentally tractable systems. Although the above strategies have been demonstrated in animal development and stem cell research, much care and effort are still required to implement these methods. Here we review the development of single-cell lineage tracing, major characteristics of the cell barcoding strategies, applications, as well as technical considerations and limitations, providing a guide to choose or improve the single-cell barcoding lineage tracing.