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Q＆A

What is your hot research topic?

I am interested in understanding how three-dimensional (3D) genome organization, which underlies various genome functions including gene expression, is spatiotemporally regulated. We approach this question through the lens of DNA replication timing, which is closely linked to 3D genome organization. Our studies have revealed that both 3D genome organization and DNA replication control exhibit remarkable plasticity across developmental stages and cell types, and that these changes are strongly coordinated, suggesting that the two processes may themselves be coordinately regulated. Moving forward, with a particular focus on early mouse embryos, we aim to uncover the molecular basis and biological significance of this flexibility and coordination, and ultimately understand how diverse cell types properly execute genome functions while stably maintaining and transmitting their genomes.

Have you had any breakthroughs or significant research progress in the last 5 years?

Together with our collaborators, we extended the genome-wide DNA replication timing profiling method I had previously developed to establish scRepli-seq, a single-cell DNA replication sequencing method, in 2019 (Takahashi et al., Nat Genet 2019). This unique approach enables us to characterize DNA replication dynamics during development and differentiation at the single-cell level and to infer changes in 3D genome organization from these dynamics. Using ES cell differentiation, early mouse embryogenesis, and X-chromosome inactivation as model systems, we have discovered that DNA replication control is far more diverse and flexible than previously thought (Miura et al., Nat Genet 2019; Poonperm et al., Nat Struct Mol Biol 2023; Takahashi et al., Nature 2024). More recently, we found that the establishment of orderly 3D chromosome organization at the G1/S transition after cell division plays an important role in controlling DNA replication in the subsequent S phase (Oji et al., Nat Commun 2026).

What kind of background do your lab members have?

Many of our members have backgrounds in the life sciences, but we also have people with different academic backgrounds as well as members from overseas, making us a diverse research group. Our research combines a variety of approaches, ranging from experimental biology to genomics and bioinformatics.

Do you collaborate with other institutions and universities?

We collaborate with many laboratories in Japan and around the world through joint research projects. In addition to large scientific conferences, we actively participate in small- to medium-sized research meetings, which I personally enjoy the most! We also organize such meetings ourselves. More recently, we have been building connections with researchers in epigenetics and genome biology across Asia, including by organizing international scientific meetings.

What kind of careers do your lab's alumni go on to?

Many of our former members have pursued careers in academia, taking positions such as university faculty members and postdoctoral researchers at institutions overseas, while others have gone on to PhD programs. Each has followed a path that reflects their own interests and career goals.

How do you develop your research?

I continue to be fascinated by the depth of genomes and chromosomes. By combining our unique technologies with the flexible and creative ideas of young researchers, I hope to deepen our understanding of genomes and chromosomes, which carry our genetic information. I am excited to see what new and interesting directions will emerge from our research, whether in basic science, applied research, or technology development.