Connecting past and present: single-cell lineage tracing

Abstract

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.

Lineage tracing reveals fate bias and transcriptional memory in human B cells

“…We speculate similar intrinsic heterogeneity and cell fate biases exist in other immune cells ( SanMiguel et al, 2020 ) but have yet to be fully described because of a lack of detailed clone tracking. In general, as lineage tracing and cell-recording technologies continue to develop, researchers will genetically record bespoke cell experiences, and use single-cell genomics to analyze their effects on intrinsic cell identities ( Chen et al, 2022 ). Finally, we note that in vitro differentiation has moved out of research labs and into the clinic in the form of CAR-T therapies and regenerative medicine efforts.…”

Fate Bias and Transcriptional Memory of human B cells

“…These differences are particularly interesting given these cell types are transcriptomically difficult to distinguish when at rest. In general, as lineage tracing and cell-recording technologies continue to develop, researchers will genetically record bespoke cell experiences, and use single-cell genomics to analyze their effects on intrinsic cell biases (Chen et al, 2022). Importantly, the intrinsic differences between B cell clones became most apparent when we subjected them to a differentiation protocol in vitro .…”

Marker-free quantification of progenitor population reveals incipient cell fate commitments

“…With the growing availability of high-quality cell phylogenies we anticipate the method would enable the quantification of lineage diversity for all tissues of a complex organism including humans. This would be fundamental to a quantitative model for understanding the between-individual developmental plasticity and the age-dependent degeneration of the tissues 49,50 .…”