scRepli-Seq: A Powerful Tool to Study Replication Timing and Genome Instability

Advances in “omics” technology have made it possible to study a wide range of cellular phenomena at the single-cell level. Recently, we developed single-cell DNA replication sequencing (scRepli-seq) that measures replication timing (RT) by copy number differences between replicated and unreplicated genomic DNA in replicating single mammalian cells. This method has been used to reveal previously unrecognized static and dynamic natures of several hundred kilobases to a few megabases-scale chromosomal units called RT domains. Because RT domains are highly correlated to A/B compartments detected by Hi-C, scRepli-seq data can be used to predict the 3D organization of the genome in the nuclear space. scRepli-seq, which essentially measures the copy number, can also be applied to study genome instability.