Recording development with single cell dynamic lineage tracing.

Aaron Mckenna,James A Gagnon,Allon Klein,Barbara Treutlein

doi:10.1242/dev.169730

Aaron Mckenna, James A Gagnon + Show 2 more

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https://doi.org/10.1242/dev.169730

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Abstract

ABSTRACTEvery animal grows from a single fertilized egg into an intricate network of cell types and organ systems. This process is captured in a lineage tree: a diagram of every cell's ancestry back to the founding zygote. Biologists have long sought to trace this cell lineage tree in individual organisms and have developed a variety of technologies to map the progeny of specific cells. However, there are billions to trillions of cells in complex organisms, and conventional approaches can only map a limited number of clonal populations per experiment. A new generation of tools that use molecular recording methods integrated with single cell profiling technologies may provide a solution. Here, we summarize recent breakthroughs in these technologies, outline experimental and computational challenges, and discuss biological questions that can be addressed using single cell dynamic lineage tracing.

Highlights

The development of plants and animals has long been a source of fascination to those interested in the construction of complex organisms
Only one locus is used in these recombinase strategies to avoid the excision of large stretches of DNA through engineered chromosome loss (Lewandoski and Martin, 1997). Both CRISPR and recombinase-based dynamic lineage tracing approaches are prospective in nature; the recording construct has to be integrated into the genome of the organism, precluding their use in humans for ethical reasons
All of the lineage tracing methods mentioned above have advantages, drawbacks and applications in modern developmental biology. In this Review, we focus on dynamic lineage tracing, which can be used to record deep branching lineage relationships

Summary

Introduction

The development of plants and animals has long been a source of fascination to those interested in the construction of complex organisms. A more recently developed approach, which we term ‘dynamic lineage tracing’ (see Glossary, Box 1), aims to diversify barcode sequences in cells during development, allowing the generation of branching lineage trees (Fig. 1E) These approaches can generate thousands of evolving sequences that can be related to each other by shared mutations (Alemany et al, 2018; Frieda et al, 2017; Junker et al, 2017 preprint; McKenna et al, 2016; Pei et al, 2017; Peikon et al, 2014; Spanjaard et al, 2018). Only one locus is used in these recombinase strategies to avoid the excision of large stretches of DNA through engineered chromosome loss (Lewandoski and Martin, 1997) Both CRISPR and recombinase-based dynamic lineage tracing approaches are prospective in nature; the recording construct has to be integrated into the genome of the organism, precluding their use in humans for ethical reasons. Barcode selection and integration Dynamic lineage tracing approaches record information at a predefined location in the genome, commonly referred to as a

E Dynamic lineage tracing

A TAC TGA TAC TGAC TG

Conclusions and perspectives