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Kyungpook National University Research Team Led by Professor Ji Won Oh Publishes Paper in “Nature” on Clonal Dynamics in Early Human Embryogenesis Inferred from Somatic Mutation

Date
2021/10/05
Writer
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Kyungpook National University’s research team led by Professor Ji Won Oh (School of Medicine) collaborated in joint research with KAIST's research team led by Professor Young Seok Ju, and succeeded in identifying clonal dynamics in early human embryogenesis using whole-genome sequencing (WGS). The results of this study were published in the online edition of Nature, a world-renowned journal, on August 25. It is currently the largest systematic study on the small number of cells in the human embryo and their constitution of the 40 trillion cells in the human body as well as their cellular differentiation into different human organs.

 

To date, research on human development, based on the destruction of embryos, has been conducted through animal experimentation with nematodes, fruit flies, and mice. However, fundamental differences in species have placed an inevitable limitation on providing a full understanding of human development.

 

To account for this limitation, the research team thereby focused on genomic mutations. As genomic mutations presumably accumulate in somatic cells throughout life, beginning with the first cell division, the team found that these mutations could systematically be analyzed and used as cellular barcodes to reconstruct developmental phylogenies of somatic cells and trace early embryonic mutations (EEM) in human individuals. Thus, the team performed the world’s largest whole-genome analysis of 334 single-cell colonies and targeted deep sequences of 379 bulk tissues donated from 7 adult human donors.

 

As a result, the team succeeded in identifying important traits of human embryonic development, such as that embryonic cells are different in nature in the beginning stages of development as well as that it is possible to identify the period of differentiation of embryonic cells into each organ-specific cell. These findings are significant because they suggest the tracing of human embryonic development using whole-genome big data without raising ethical issues. Through this method, it becomes not only possible to identify and reconstruct cellular movements that appear within each human individual, but also help prevent, screen, and develop an effective system for the treatment of rare diseases in the future.

 

This research was supported by the Ministry of Health and Welfare's World-Leading Medical Scientist Development Project, Seo Kyung-Bae Science Foundation, National Research Foundation of Korea (Leader, Excellent New Research, Excellent Local Scientist Projects), Kyungpook National University Vascular Organ Interaction Control Center (Center Director You Mie Lee), Korea Institute of Science and Technology Information (KISTI), Catholic Medical University, Genome Insight Co., Ltd., and Immune Square Co., Ltd.

 

Dr. Nanda Mali, presently a postdoctoral researcher at Kyungpook National University’s Vascular Organ Interaction Control Center, participated as the co-first author of this research. She conducted the research as a Ph.D. candidate under Professor Dongsun Kim at Kyungpook National University, in collaboration with KNU College of Medicine BK Human Resources Development Project Team (KNU Convergence Medical Life Sciences Future Creative Talent Cultivation Education Research Center).




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