Developmental Lineage Mapping by Genomic Barcoding in the Mouse

Monday, January 28, 2019 -
2:00pm to 3:00pm
The FUNG Auditorium
Reza Kalhor

Wyss Institute Research Associate in Technology Development

Department of Genetics and Wyss Institute

Harvard Medical School

Developmental Lineage Mapping by Genomic Barcoding in the Mouse

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 an effective means of generating DNA barcodes with a high and scalable diversity. We further describe the implementation of this system in a mouse model with multiple genomically-integrated 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 resulted in developmentally barcoded embryos wherein information about each cell's lineage was recorded in its genome. We used these recordings to reconstruct early developmental lineages in the mouse and determine the order of axis specification in its brain. Our results provide an enabling and versatile platform for in vivo barcoding and lineage tracing in a mammalian model system.

Bio: 

Reza Kalhor is a Wyss Institute Research Associate in Technology Development and a member of George Church’s group at Harvard Medical School. He is interested in using DNA as a medium for storing digital and biological information. His current work is focused on utilizing the genome for recording developmental events in mammalian embryos.