Journal
SCIENCE
Volume 358, Issue 6369, Pages 1457-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aao0958
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Funding
- Department of Defense Office of Naval Research [N00014-17-1-2353, N00014-15-1-2704]
- NIH Director's Early Independence Award [DP50D009172-02]
- Sloan Foundation [FR-2015-65795]
- Fannie and John Hertz Foundation
- NSF [DGE 16-44869]
- NIH [T32GM008224]
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Although dynamics underlie many biological processes, our ability to robustly and accurately profile time-varying biological signals and regulatory programs remains limited. Here we describe a framework for storing temporal biological information directly in the genomes of a cell population. We developed a biological tape recorder in which biological signals trigger intracellular DNA production that is then recorded by the CRISPR-Cas adaptation system. This approach enables stable recording over multiple days and accurate reconstruction of temporal and lineage information by sequencing CRISPR arrays. We further demonstrate a multiplexing strategy to simultaneously record the temporal availability of three metabolites (copper, trehalose, and fucose) in the environment of a cell population over time. This work enables the temporal measurement of dynamic cellular states and environmental changes and suggests new applications for chronicling biological events on a large scale.
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