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A homing CRISPR mouse resource for barcoding and lineage tracing

View ORCID ProfileReza Kalhor, Kian Kalhor, Kathleen Leeper, Amanda Graveline, Prashant Mali, George M. Church
doi: https://doi.org/10.1101/280289
Reza Kalhor
1Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
2Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
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  • ORCID record for Reza Kalhor
Kian Kalhor
3Department of Electrical Engineering, Sharif University of Technology, Tehran, Iran.
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Kathleen Leeper
2Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
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Amanda Graveline
2Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
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Prashant Mali
4Department of Bioengineering, University of California San Diego, La Jolla, California, USA.
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George M. Church
1Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
2Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
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Abstract

Cellular barcoding using nuclease-induced genetic mutations is an effective approach that is emerging for recording biological information, including developmental lineages. We have previously introduced the homing CRISPR system as a promising methodology for generating such barcodes with scalable diversity and without crosstalk. Here, we present a mouse line (MARC1) with multiple genomically-integrated and heritable homing guide RNAs (hgRNAs). We determine the genomic locations of these hgRNAs, their activity profiles during gestation, and the diversity of their mutants. We apply the line for unique barcoding of mouse embryos and differential barcoding of embryonic tissues. We conclude that this mouse line can address the unique challenges associated with in vivo barcoding in mammalian model organisms and is thus an enabling platform for recording and lineage tracing applications in a mammalian model system.

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Posted March 12, 2018.
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A homing CRISPR mouse resource for barcoding and lineage tracing
Reza Kalhor, Kian Kalhor, Kathleen Leeper, Amanda Graveline, Prashant Mali, George M. Church
bioRxiv 280289; doi: https://doi.org/10.1101/280289
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A homing CRISPR mouse resource for barcoding and lineage tracing
Reza Kalhor, Kian Kalhor, Kathleen Leeper, Amanda Graveline, Prashant Mali, George M. Church
bioRxiv 280289; doi: https://doi.org/10.1101/280289

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