TY - JOUR T1 - Whole organism lineage tracing by combinatorial and cumulative genome editing JF - bioRxiv DO - 10.1101/052712 SP - 052712 AU - Aaron McKenna AU - Gregory M. Findlay AU - James A. Gagnon AU - Marshall S. Horwitz AU - Alexander F. Schier AU - Jay Shendure Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/05/11/052712.abstract N2 - Multicellular systems develop from single cells through a lineage, but current lineage tracing approaches scale poorly to whole organisms. Here we use genome editing to progressively introduce and accumulate diverse mutations in a DNA barcode over multiple rounds of cell division. The barcode, an array of CRISPR/Cas9 target sites, records lineage relationships in the patterns of mutations shared between cells. In cell culture and zebrafish, we show that rates and patterns of editing are tunable, and that thousands of lineage-informative barcode alleles can be generated. We find that most cells in adult zebrafish organs derive from relatively few embryonic progenitors. Genome editing of synthetic target arrays for lineage tracing (GESTALT) will help generate large-scale maps of cell lineage in multicellular systems. ER -