Harvard Medical School
Dept. of Genetics
Developmental lineage mapping by genomic barcoding in the mouse
Monday, January 7
2 PM
RRI 101
Abstract: Cellular barcoding using nuclease-induced DNA mutations is an effective approach that is emerging for recording biological information, including developmental lineages. We introduce the homing CRISPR system as a promising methodology for generating such barcodes with scalable diversity and without crosstalk. We also describe a mouse line with multiple genomically-integrated and heritable homing guide RNAs (hgRNAs).
Each hgRNA can generate hundreds of mutant alleles which combine exponentially to create a large number of barcodes. Activating these hgRNAs at conception results in developmentally barcoded embryos wherein information about each cell's lineage is recorded in its genome.
As a proof-of-principle, we use these barcodes to reconstruct mouse developmental lineages from the earliest stages. We further evaluate the properties of hgRNA-based lineage recordings and show that partial recordings from different hgRNAs can be integrated to reconstruct the information.
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