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New 'genetic barcode' technique reveals details of cell lineage

American Association for the Advancement of Science


IMAGE: Genome editing of synthetic target arrays for lineage tracing (GESTALT) can be used to generate largescale maps of cell lineage. This material relates to a paper that appeared in the... view more

Credit: James Gagnon

By using the gene editing tool CRISPR to create unique genetic "barcodes," it's possible to track the lineage of cells in a living organism, a new study reveals. The development could accelerate our understanding of an array of cellular processes. While several different methods exist for tracking cell lineages, each has limitations. For example, dyes may be used to track the creation of daughter cells, but do not provide insights into the relationships between the descendent cells. Here, Aaron McKenna and colleagues developed a lineage tracing method called Genome Editing of Synthetic Target Arrays for Lineage Tracing (GESTALT). The method introduces unique patterns of mutations into a distinct, short genetic sequence called a genomic barcode. The DNA sequence of mutated barcodes in daughter cells is then used to reconstruct cell lineage relationships. McKenna et al. demonstrate the efficacy of this technique in cell culture and live zebrafish. Upon introducing bar codes at the embryonic stage of zebrafish and analyzing various tissues at the adult stage, the researchers found that just a few embryonic progenitor cells give rise to the majority of cells that make up adult organs. For example, only 5 of the 1,138 gene variants observed in a four-month-old zebrafish gave rise to more than 98% of blood cells. The authors note that this new technique can be used in future analyses to track more complex, multicellular processes in normal development, and that it can also be used to identify the cellular origin of tumors and metastases.


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