Establishment of a new methodology for inducing early embryo-like structures from stem cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04799
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Kyoto University (2017-2018); Institute of Physical and Chemical Research (2016)
• Principal Investigator: Eiraku Mototsugu 京都大学, ウイルス・再生医科学研究所, 教授 (40415097)
• Research Collaborator: Takata Nozomu ; Okuda Satoru
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: モルフォゲン / オルガノイド / 幹細胞

Outline of Final Research Achievements

We have developed a system that can generate artificial substance concentration gradients with high spatial and temporal freedom in organoids culture. Using this system, morphogen factors such as BMP, Wnt, Activin, etc. were locally applied under imaging. As a result, we succeeded in inducing ESC-derived organoids with a primitive streak-like structure. The induced organoids exhibited a structure similar to the early embryo, in which the tissues derived from the three germ layers were orderly positioned. Additionally, it was revealed by calcium imaging and statistical analysis that the future differentiation patterns can be predicted from a pattern of spontaneous intracellular calcium transients in a early differentiating ESC aggregate.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、胚葉体に対して人為的にモルフォゲン勾配を安定的に作用させるための新規技術を確立した。これにより、より複雑な組織構造や分化パターンを持つオルガノイド を形成できる可能性を開いた。また三胚葉由来の組織を同時に一つのオルガノイド中に形成させることにより、より生体の個体発生過程に似た分化様式を再現することができる。今後はヒト多能性幹細胞にも応用することにより、再生医療や創薬スクリーニングの開発に寄与することが期待される。