Dr. Jay Shendure, Lead Scientific Director for Seattle Hub
[Editor’s note: The following is a series of excerpts from “The lives of cells, recorded,” a perspective piece published in Nature Reviews Genetics. Authors include BBI’s Dr. Jay Shendure, whose work leading the Seattle Hub for Synthetic Biology is reflected in the article.]
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...
Building on a rich history, the nascent field of DNA-based recording offers a potential way of obtaining cellular histories that overcomes the limitations of current measurement paradigms. The basic premise of DNA-based recording is to engineer cells to record their histories into their genomes using DNA editors, such that a single destructive snapshot is informative with respect to not only each cell’s present but also its past…
We envision that recent technological advances in DNA-based recording, coupled with overcoming these challenges, will enable the routine recording of cellular histories. This approach will further our understanding of cell decisions over time, given their cellular ancestry and past cell trajectories, and in response to external signals and spatial context. Comparative analyses of such data will enable the deduction of general rules of cell decisions in development and disease. Looking ahead, when recordings can be coupled to responses, such technologies will offer unique opportunities within synthetic biology, in both basic research and in translation to medical applications.
Read the full article here.