This review systematically summarizes how DNA recording technologies enable long-term storage of cellular lineage, signals, states, and spatial information within the genome, offering a novel dynamic perspective for developmental and disease research.
Literature Overview
The article, 'The lives of cells, recorded,' published in Nature Reviews Genetics, reviews and summarizes recent advances in DNA-based molecular recording technologies in cell biology. It systematically explains how cellular historical information—including lineage relationships, external signals, internal states, and spatial positions—can be written into the genome using gene-editing tools. The article also discusses how single-cell sequencing and spatial omics technologies can be used to read this information, enabling the reconstruction of complete cellular histories through computational and phylogenetic algorithms. This technology promises to overcome the limitations of traditional static measurement methods, enabling dynamic dissection of development, regeneration, and disease progression. The article further outlines current challenges and future directions.Background Knowledge
Cell fate determination, tissue development, and disease evolution are central questions in biology. Traditional studies rely on static sampling or live imaging, which struggle to comprehensively capture the dynamic history of cells. In recent years, single-cell omics technologies have revealed cellular heterogeneity but cannot directly trace developmental trajectories. DNA recording technologies have emerged to address this gap, using heritable genomic edits as a 'molecular pen' to continuously record information during cell division and environmental responses. This approach integrates synthetic biology, genome editing, and computational biology, and has already enabled lineage tracing in model organisms. However, achieving high-precision, multidimensional, and long-term information recording, as well as efficiently reading and reconstructing complex histories, remains a major challenge. This article systematically reviews various writing strategies (e.g., recombinases, CRISPR, reverse transcriptase systems), readout methods (sequencing and imaging), and reconstruction algorithms, clarifying current technical bottlenecks and breakthrough directions, thus providing a novel tool framework for understanding cell fate regulation mechanisms.
Research Methods and Experiments
The authors review the principles and applications of various DNA recording systems, including site-specific recombinase-based systems (e.g., intMEMOIR), CRISPR-Cas9-mediated DNA 'scar' recording, base editing, and reverse transcriptase integration systems (e.g., Cas1–Cas2-RT). These systems can record lineage information during cell division or perform conditional editing in response to specific signals (e.g., transcription factor activity, signaling pathway activation). The recorded information can be retrieved via single-cell RNA sequencing, long-read sequencing, or spatial imaging techniques. Combined with phylogenetic reconstruction algorithms, they allow inference of cell lineage trees, 'decorated' with dynamic signals and spatial data, thereby constructing multidimensional cell history maps. The article also discusses the potential of prime editors for enabling ordered recording and frameworks like ENGRAM for transcript event recording.Key Conclusions and Perspectives
Research Significance and Prospects
DNA recording technology represents a paradigm shift from static 'snapshots' to dynamic 'videos,' potentially reconstructing the complete developmental and evolutionary history of biological systems at single-cell resolution. Future optimized recording systems will achieve higher information density, longer recording durations, and broader biological orthogonality, enabling the construction of four-dimensional cell atlases when combined with spatial omics.
In basic research, this technology can be used to dissect organ development, tissue regeneration, and tumor heterogeneity, while in translational medicine, it can monitor treatment responses and microenvironmental changes. Despite ongoing technical and computational challenges, its potential is immense and will profoundly reshape our understanding of cell fate decisions and disease progression.
Conclusion
This article provides a comprehensive review of the principles, progress, and application prospects of DNA recording technology, emphasizing its revolutionary potential in deciphering the life history of cells. By encoding lineage, signals, states, and spatial information into the genome, this technology enables dynamic tracing of development and disease processes. Multiple editing systems have demonstrated recording capabilities in diverse biological contexts, and when combined with single-cell and spatial omics technologies, can reconstruct high-resolution cellular history maps. Despite ongoing challenges in recording capacity, orthogonality, readout efficiency, and algorithmic precision, the field is advancing rapidly. In the future, DNA recording is expected to become a standard tool for studying dynamic behaviors in complex biological systems, offering unprecedented spatiotemporal resolution for developmental biology, cancer research, and microbial ecology. This technology not only deepens our understanding of life processes but also provides a novel perspective for dissecting disease mechanisms and developing therapeutic strategies. In summary, DNA recording is ushering in a new era of recording and replaying the life journeys of cells.
