Retrospective Lineage Tracing: An Optimal Approach for the Study of Intrinsic Cellular Development

Lineage tracing is an essential tool for understanding cellular development and tissue dynamics. This review examines retrospective lineage tracing as an optimal approach for studying cellular development and contrasts retrospective with prospective lineage tracing methods. Retrospective lineage tracing approaches leverage naturally occurring genetic barcodes, such as single nucleotide polymorphisms (SNPs), copy number variants (CNVs), and mitochondrial DNA mutations, which enables the detailed reconstruction of cell lineages without prior genetic manipulation. Researchers can ultimately infer developmental trajectories and clonal relationships across hematopoiesis and tumorigenesis by analyzing these endogenous markers. This paper considers how retrospective lineage tracing methods circumvent the limitations of prospective approaches, such as the need for exogenous labeling, and is valuable for studying human hematopoiesis.