A new discovery by researchers at the RIKEN Center for Biosystems Dynamics (BDR) in Japan upends decades of assumptions regarding DNA replication. Led by Ichiro Hiratani and colleagues, the experiments published August 28 in Nature show that DNA replication in early embryos is different from what past research has taught, and includes a period of instability that is prone to chromosomal copying errors. As failed pregnancies and developmental disorders are often related to chromosomal abnormalities the findings could impact the field of reproductive medicine, perhaps leading to improved methods of in vitro fertilization (IVF).

During embryogenesis, the initially fertilized egg divides, as do each new set of daughter cells. By the third day after fertilization, an embryo has undergone three divisions and contains 16 cells. Each cell division is accompanied by DNA replication, ensuring that each daughter cell contains a copy of the whole genome.

In their new study, the team of RIKEN BDR researchers set out to characterize the nature of the DNA replication process in early-stage embryos. They used their homemade single-cell genomics technique called scRepli-seq and applied it to developing mouse embryos. With this technology, the team was able to take snapshots of single embryonic cell DNA at different times during the DNA-replication periods.

What they found contradicted what scientists have assumed about DNA replication in embryos. We found multiple specialized types of DNA rep.