World-first research: bringing more insights into biodiversity -- A new technique to analyze genomic functions of wild and extinct animals -- Kindai University

A research team lead by Associate Professor Kei Miyamoto of Kindai University (Faculty of Biology-Oriented Science and Technology, Kinokawa city, Wakayama, Japan) and Cambridge University (UK) jointly developed a new technique to induce reprogramming*1 of genomes in mammals.

This technique was developed by modifying the conventional cloning technology*2 and is the world’s first successful induction of gene activation*3, which is specifically expressed in early embryos from genomes of Oryx dammah, now extinct in the wild. In the past, examining DNA base sequence was the mainstream technique to analyze wildlife genomes.　This new method makes it possible to analyze how genome sequences function in various　animals, including extinct species, which is a significant achievement to understand biodiversity.

This research was published in “iScience”, an open-access journal from Cell Press.

URL：https://www.cell.com/iscience/fulltext/S2589-0042(21)01259-1

1. Key points

- Developed a new method that induces the reprogramming of the mammalian genome, including wild/endangered species, and induces the activation of genes that are specifically expressed in early embryos.

- This allows induction of reprogramming of various animal cell nuclei, which was difficult with conventional cloning methods.

- This significant result brings insights into biodiversity, allowing analysis of genomic functions of extinct animals.

2. Details of the research

Various cloned animals have been created with the reprogramming technology that restores cells to the undifferentiated state by transplanting differentiated adult somatic cells into oocytes, and it has been also expected to revive endangered or extinct species. However, most cloning techniques are limited to lab animals that can be reproductively controlled in the laboratory, and thus it is considered difficult to induce reprogramming in wild animals.

The research team succeeded in inducing the activation of embryonic genes*4, which is an essential reprogramming phenomenon, with various animal somatic nuclei in mouse embryos arrested at the early stage, which has not been used in conventional cloning techniques. By this technique, the team established primary cultured cells using tissues collected from postmortem Oryx dammah, a species extinct in the wild, and succeeded in activating embryonic genes from their cell nuclei. The findings of this research will enable analysis of genomic functions of various wild animals using laboratory mouse embryos.

The new cloning technology developed in this research will make it possible to analyze the functions of the endangered or extinct animal genomes. This will give us insights into biodiversity to elucidate the characteristics related to the extinction of species at the molecular level.

3. About publication

Journal name:
iScience（Impact factor: 5.458）

Research paper title:
Cell division- and DNA replication-free reprogramming of somatic nuclei for embryonic transcription

Authors:
Junko Tomikawa (Research Assistant, Faculty of Biology-Oriented Science and Technology, Kindai University), Christopher A. Penfold (Postdoctoral Researcher, Cambridge University), Takuma Kamiya (Major in Biotechnological Science, Graduate School of Biology-Oriented Science and Technology, Kindai University, Graduated in 2020), Risa Hibino (Department of Genetic Engineering, Faculty of Biology-Oriented Science and Technology, Kindai University, Graduated in 2021), Ayumi Kosaka (Department of Genetic Engineering, Faculty of Biology-Oriented Science and Technology, Kindai University, Graduated in 2021), Masayuki Anzai (Professor, Institute of Advanced Technology, Kindai University), Kazuya Matsumoto (Professor, Faculty of Biology-Oriented Science and Technology, Kindai University), Kei Miyamoto (Associate Professor, Faculty of Biology-Oriented Science and Technology, Kindai University)

Corresponding authors:
Kei Miyamoto

Co-first authors:
Junko Tomikawa, Christopher A. Penfold, Takuma Kamiya

4. Glossary

*1 Reprogramming: Reprogramming is the process that adult somatic cells acquire the ability to differentiate into all cell types of an organism. In particular, genomic reprogramming resets the epigenetic information accumulated in the adult somatic cells, and the cells revert back to an early embryonic state.

*2 Cloning technology: Development of reconstructed embryos produced by transplanting cell nuclei into pre-fertilized eggs is induced by activation stimulation, and then the reconstructed embryos are to be implanted in oocytes to generate cloned animals that share identical genomes as the donor cells.

*3 Gene activation (Gene expression)：This is a process in which the expression of a gene is triggered in the cell and RNA and protein are synthesized.

*4 Embryonic gene：A gene that is expressed in preimplantation embryos in the very early state. This is essential for normal embryonic development.