Mapping single-cell-resolution cell phylogeny reveals cell population dynamics during organ developments

Mapping the cell phylogeny of a complex multicellular organism relies on somatic mutations accumulated from zygote to adult. Available cell barcoding methods can only record no more than four mutations per barcode, enabling a low-resolution mapping of the cell phylogeny of a complex organism. We here developed SMALT, a substitution mutation aided lineage tracing system that outperforms the available cell barcoding methods in mapping cell phylogeny. We applied SMALT to Drosophila melanogaster and obtained on average over 20 mutations on a three kilobase-pair barcoding sequence in early-adult cells.