Multiplex recording of cellular events over time on CRISPR biological tape

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Science  15 Dec 2017:
Vol. 358, Issue 6369, pp. 1457-1461
DOI: 10.1126/science.aao0958

A CRISPR device to record time

The CRISPR adaptation system has been used to record the sequence and ordering of exogenous oligonucleotides that are electroporated into cell populations. Sheth et al. engineered a system bypassing the use of exogenous DNA to directly record temporal signals. An input biological signal is transformed into the ratio of the frequency of incorporating trigger DNA to that of incorporating reference DNA into the genomes of a bacterial population. A multiplexing strategy enables simultaneous recording of three environmental signals with high temporal resolution.

Science, this issue p. 1457


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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