Research Article

Developmental barcoding of whole mouse via homing CRISPR

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Science  09 Aug 2018:
eaat9804
DOI: 10.1126/science.aat9804

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Abstract

In vivo barcoding using nuclease-induced mutations is a powerful approach for recording biological information, including developmental lineages; however, its application in mammalian systems has been limited. We present in vivo barcoding in the mouse with multiple homing guide RNAs that each generate hundreds of mutant alleles and combine for an exponential diversity of barcodes. Activation upon conception and continued mutagenesis through gestation result in developmentally barcoded mice wherein information is recorded in lineage-specific mutations. We use these recordings for reliable post hoc reconstruction of the earliest lineages and investigating axis development in the brain. Our results provide an enabling and versatile platform for in vivo barcoding and lineage tracing in a mammalian model system.

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