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Developmental barcoding of whole mouse via homing CRISPR.

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 to produce an exponential diversity of barcodes. Activation upon conception and continued mutagenesis through gestation resulted in developmentally barcoded mice wherein information is recorded in lineage-specific mutations. We used these recordings for reliable post hoc reconstruction of the earliest lineages and investigation of 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.

SUBMITTER: Kalhor R

PROVIDER: S-EPMC6139672 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Developmental barcoding of whole mouse via homing CRISPR.

Kalhor Reza R Kalhor Kian K Mejia Leo L Leeper Kathleen K Graveline Amanda A Mali Prashant P Church George M GM Church George M GM

Science (New York, N.Y.) 20180809 6405

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 to produce an exponential diversity of barcodes. Activation upon conception and continued mutagenesis through gestation resulted in developmentally barcoded m ...[more]

PMID: 30093604

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