Bio-Rad - Preparing for a Stress-free QC Audit

Artificial cell nuclei created in living mouse eggs

Researchers from Kindai University and collaborating institutions have achieved a significant milestone in cell biology by creating artificial cell nuclei within living mouse eggs. The study, published in the journal Genes to Cells [1], demonstrates for the first time that functional nuclei can be constructed by injecting purified DNA solution into oocytes, mimicking the fertilisation process.

Understanding nuclear formation

The cell nucleus, a crucial organelle involved in DNA replication and transcription, has long been a subject of intense study. However, the precise mechanisms underlying nuclear formation and the factors required for its functionality have remained elusive. This groundbreaking research sheds new light on these fundamental questions.

Professor Kazuo Yamagata from Kindai University’s Faculty of Biology-Oriented Science and Technology, who led the study, explained the significance of their findings: “By injecting purified DNA instead of sperm at the appropriate timing, we were able to carry out a fertilisation-like process and construct a structure very similar to a real nucleus.”

artifical cell nucleus

The artificial cell nucleus (right) constructed using the purified DNA was morphologically very similar to the natural cell nucleus derived from an egg (left).
(Prof. Kazuo Yamagata from Kindai University)

Optimizing DNA injection

The research team discovered that the behaviour of the injected DNA varied depending on its length and concentration. Through careful experimentation, they determined the optimal parameters for successful nuclear formation.

“We found that both the length and concentration of the injected DNA were critical factors in achieving successful nuclear construction,” said Professor Tokuko Haraguchi from Osaka University’s Graduate School of Frontier Biosciences, a co-leader of the study.

Verifying nuclear structures and functions

To confirm the authenticity of the artificial nuclei, the researchers conducted a series of detailed observations and analyses. They verified that the injected DNA formed a nucleosome structure, a key feature of eukaryotic chromosomes. Additionally, they observed the formation of a nuclear membrane and nuclear pore complexes surrounding the injected DNA, closely resembling those found in natural nuclei.

Importantly, the team also confirmed that the artificial nuclei possessed sufficient transport function, a crucial aspect of nuclear functionality. This was achieved through live cell imaging techniques, allowing the researchers to capture the process of nuclear pore complex acquisition by the injected DNA in real-time.

Implications for future research

The successful creation of artificial cell nuclei with nuclear transport functions opens up exciting possibilities for future research. Dr Nao Yonezawa, a doctoral student at Kindai University and first author of the study, commented on the potential applications: “This breakthrough could pave the way for more advanced studies on nuclear formation and function, potentially leading to new technologies in areas such as the revival of extinct animals or the creation of artificial life.”

Collaborative effort

The study was the result of a collaborative effort involving researchers from multiple institutions. In addition to Kindai University and Osaka University, the team included scientists from Keio University School of Medicine and Tokyo Institute of Technology.

This multidisciplinary approach allowed the researchers to leverage a wide range of expertise and technologies, contributing to the success of the project.

This research provides a solid foundation for further investigations into nuclear formation and function. The ability to construct artificial nuclei in living cells offers a unique tool for studying the fundamental processes of life at the molecular level.

While the potential applications of this technology are exciting, the researchers caution that much work remains to be done before practical applications can be realized. Nonetheless, this study represents a significant step forward in our understanding of one of the most crucial components of eukaryotic cells.

Reference:
1. Yonezawa, N., Shindo, T., Oda, H., et. al. (2024). Reconstruction of artificial nuclei with nuclear import activity in living mouse oocytes. Genes to Cells. https://doi.org/10.1111/gtc.13149