UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Salvador-Martínez, I; Grillo, M; Averof, M; Telford, MJ; (2018) Is it possible to reconstruct an accurate cell lineage using CRISPR recorders? BioRxiv: Cold Spring Harbor, NY, USA. Green open access

[thumbnail of Salvador-Martínez_bioRxiv_2018.pdf]
Preview
Text
Salvador-Martínez_bioRxiv_2018.pdf - Submitted Version

Download (4MB) | Preview

Abstract

Cell lineages provide the framework for understanding how multicellular organisms are built and how cell fates are decided during development. Describing cell lineages in most organisms is challenging, given the number of cells involved; even a fruit fly larva has ~50,000 cells and a small mammal has more than 1 billion cells. Recently, the idea of using CRISPR to induce mutations during development as heritable markers for lineage reconstruction has been proposed and trialled by several groups. While an attractive idea, its practical value depends on the accuracy of the cell lineages that can be generated by this method. Here, we use computer simulations to estimate the performance of this approach under different conditions. Our simulations 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 mutation sequencing strategies. Our approach reveals the limitations of recently published CRISPR recorders, and indicates how future implementations can be optimised to produce accurate cell lineages.

Type: Working / discussion paper
Title: Is it possible to reconstruct an accurate cell lineage using CRISPR recorders?
Open access status: An open access version is available from UCL Discovery
DOI: 10.1101/373357
Publisher version: https://doi.org/10.1101/373357
Language: English
Additional information: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices
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/10075572
Downloads since deposit
7Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item