Understanding the molecular basis that defines species-specific developmental timing

2020 Fiscal Year Final Research Report

• Project Area: Interplay of developmental clock and extracellular environment in brain formation
• Project/Area Number: 16H06485
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University (2017-2020); 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)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: 形態形成 / 多能性幹細胞 / 種特異的発生様式

Outline of Final Research Achievements

In this study, we attempted to elucidate the molecular mechanisms that define species-specificity in development using tissue induction systems from pluripotent stem cells. We established mouse and human cerebral and retinal organoid systems and performed sequential single-cell RNA-seq to compare the dynamics of cell differentiation during development. As a result, we identified novel cells that specifically contribute to the mouse retinal formation process and their roles in morphogenesis. In addition, we identified a novel neural progenitor cell type that specifically exists in the process of human retinal tissue formation. In addition, we developed the means to induce limb bud tissue from pluripotent stem cells.

Free Research Field

発生生物学、幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

世界で初めてマウス多能性幹細胞から自己組織化により試験管内で肢芽組織を誘導する技術を開発した。ヒトを含む霊長類由来多能性幹細胞からも同様の肢芽様組織が可能となっており、失った手指の再生応用だけでなく肢芽組織の種特異性の研究への貢献が期待される。また、将来の四肢欠損の再生医療の基盤技術という点でも社会的意義は大きい。さらに、新たにマウス及びヒト網膜発生において種特異的に存在する細胞種及び遺伝子マーカーを複数同定し、これらの機能解析により種特異的な神経組織形成機構の一端が明らかになった。これらの発見をもとに、発生時間の種特異性についての分子基盤の理解が深まることが期待される。