The lives of cells, recorded

Creators: Askary, Amjad¹; Chen, Wei²; Choi, Junhong^{2, 3}; Du, Lucia Y.^{4, 2}; Elowitz, Michael B.⁵; Gagnon, James A.⁶; Schier, Alexander F.^{4, 2}; Seidel, Sophie^{7, 8}; Shendure, Jay^{2, 9, 10}; Stadler, Tanja^{7, 8}; Tran, Martin⁵

1. University of California, Los Angeles
2. University of Washington
3. Memorial Sloan Kettering Cancer Center
4. University of Basel
5. California Institute of Technology
6. University of Utah
7. ETH Zurich
8. Swiss Institute of Bioinformatics
9. Howard Hughes Medical Institute
10. Seattle Hub for Synthetic Biology, Seattle, WA, USA

Abstract

A paradigm for biology is emerging in which cells can be genetically programmed to write their histories into their own genomes. These records can subsequently be read, and the cellular histories reconstructed, which for each cell could include a record of its lineage relationships, extrinsic influences, internal states and physical locations, over time. DNA recording has the potential to transform the way that we study developmental and disease processes. Recent advances in genome engineering are driving the development of systems for DNA recording, and meanwhile single-cell and spatial omics technologies increasingly enable the recovery of the recorded information. Combined with advances in computational and phylogenetic inference algorithms, the DNA recording paradigm is beginning to bear fruit. In this Perspective, we explore the rationale and technical basis of DNA recording, what aspects of cellular biology might be recorded and how, and the types of discovery that we anticipate this paradigm will enable.

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Acknowledgement

The authors thank all members of the Allen Discovery Center for Cell Lineage Tracing, past and present, for valuable discussions over the course of the past six years. We also thank O. Oseth for extensive assistance in coordinating this collaborative writing project. This work was supported by the Paul G. Allen Frontiers Foundation (J.S., M.B.E. and A.F.S.), the National Eye Institute (R00EY031782 to A.A.), the National Institute of General Medical Sciences (R35GM142950 to J.A.G.), the UCLA BSCRC Transformative Technology Development Award (A.A.) and The Rose Hills Foundation (A.A.). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation programme (grant agreement number 101001077 to T.S. and 834788 to A.F.S.). M.E. and J.S. are Investigators of the Howard Hughes Medical Institute.

Contributions

These authors contributed equally: Amjad Askary, Wei Chen, Junhong Choi, Lucia Y. Du, Sophie Seidel, Martin Tran.

Conflict of Interest

A.A., W.C., J.C., M.B.E. and J.S. have patents related to DNA-based molecular recording. J.S. is a scientific advisory board member, consultant and/or co-founder of Cajal Neuroscience, Guardant Health, Maze Therapeutics, Camp4 Therapeutics, Phase Genomics, Adaptive Biotechnologies, Scale Biosciences, Sixth Street Capital, Prime Medicine, Somite Therapeutics and Pacific Biosciences. M.B.E. is a scientific advisory board member, consultant and/or co-founder of Primordium Labs, TeraCyte, Spatial Genomics, and Asymptote Genetic Medicines. The other authors declare no competing interests.

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