Barcodes based on nucleic acid sequences: Applications and challenges (Review).

Cells are the fundamental structural and functional units of living organisms and the study of these entities has remained a central focus throughout the history of biological sciences. Traditional cell research techniques, including fluorescent protein tagging and microscopy, have provided preliminary insights into the lineage history and clonal relationships between progenitor and descendant cells. However, these techniques exhibit inherent limitations in tracking the full developmental trajectory of cells and elucidating their heterogeneity, including sensitivity, stability and barcode drift. In developmental biology, nucleic acid barcode technology has introduced an innovative approach to cell lineage tracing. By assigning unique barcodes to individual cells, researchers can accurately identify and trace the origin and differentiation pathways of cells at various developmental stages, thereby illuminating the dynamic processes underlying tissue development and organogenesis. In cancer research, nucleic acid barcoding has played a pivotal role in analyzing the clonal architecture of tumor cells, exploring their heterogeneity and resistance mechanisms and enhancing our understanding of cancer evolution and inter‑clonal interactions. Furthermore, nucleic acid barcodes play a crucial role in stem cell research, enabling the tracking of stem cells from diverse origins and their derived progeny. This has offered novel perspectives on the mechanisms of stem cell self‑renewal and differentiation. The present review presented a comprehensive examination of the principles, applications and challenges associated with nucleic acid barcode technology.