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Is it possible to reconstruct an accurate cell lineage using CRISPR recorders?

Salvador-Martínez, I; Grillo, M; Averof, M; Telford, MJ; (2019) Is it possible to reconstruct an accurate cell lineage using CRISPR recorders? Elife , 8 , Article e40292. 10.7554/eLife.40292. Green open access

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Abstract

Cell lineages provide the framework for understanding how cell fates are decided during development. Describing cell lineages in most organisms is challenging; even a fruit fly larva has ~50,000 cells and a small mammal has >1 billion cells. Recently, the idea of applying CRISPR to induce mutations during development, to be used as heritable markers for lineage reconstruction, has been proposed by several groups. While an attractive idea, its practical value depends on the accuracy of the cell lineages that can be generated. Here, we use computer simulations to estimate the performance of these approaches under different conditions. We incorporate empirical data on CRISPR-induced mutation frequencies in Drosophila. We show significant impacts from multiple biological and technical parameters - variable cell division rates, skewed mutational outcomes, target dropouts and different sequencing strategies. Our approach reveals the limitations of published CRISPR recorders, and indicates how future implementations can be optimised. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Type: Article
Title: Is it possible to reconstruct an accurate cell lineage using CRISPR recorders?
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.40292
Publisher version: https://doi.org/10.7554/eLife.40292.001
Language: English
Additional information: © 2019, Salvador-Martínez et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
Keywords: CRISPR-based lineage recorders, D. melanogaster, cell lineage, computer simulation, developmental biology, zebrafish
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10067020
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