Askary, A. et al. Nat. Biotechnol. https://doi.org/10.1038/s41587-019-0299-4 (2019).

DNA barcoding technologies have been applied in profiling cell identities and recording dynamic biological information. In the developmental system, the continuous editing of barcodes can be used as a unique identifier for reconstructing developmental lineage. However, in situ readout of barcode edits with spatial information remains challenging. Askary et al. introduce Zombie, an approach that enables in situ imaging-based readout of DNA barcodes with sensitivity comparable to that of sequencing approaches. Zombie uses phage RNA polymerases to transcribe a DNA barcode that is downstream of a phage promoter and integrated in the genome of fixed cells. They then use single-molecule FISH or hybridization chain reaction to detect the amplified RNA products as an optical measurement of the DNA barcodes. Zombie can resolve single nucleotide differences and has been applied in chick embryos and adult mouse brain tissues for SNV detection.