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Science. 2018 Aug 31;361(6405). pii: eaat9804. doi: 10.1126/science.aat9804. Epub 2018 Aug 9.

Developmental barcoding of whole mouse via homing CRISPR.

Author information

1
Department of Genetics, Harvard Medical School, Boston, MA, USA. gchurch@genetics.med.harvard.edu kalhor@genetics.med.harvard.edu.
2
Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
3
Department of Electrical Engineering, Sharif University of Technology, Tehran, Iran.
4
Department of Genetics, Harvard Medical School, Boston, MA, USA.
5
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.

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.

PMID:
30093604
PMCID:
PMC6139672
[Available on 2019-02-28]
DOI:
10.1126/science.aat9804

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