Establishing 3-dimentional structure of trachea and esophageal organoid toward understanding the mechanism underlying mesenchymal polarization

2022 Fiscal Year Final Research Report

• Project/Area Number: 18KK0423
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
• Allocation Type: Multi-year Fund
• Research Field: Developmental biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kishimoto Keishi 国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (70700029)
• Project Period (FY): 2019 – 2022
• Keywords: オルガノイド / 気管 / 食道 / 間充織

Outline of Final Research Achievements

The trachea and esophagus are originated from a single common tube, foregut, throughout the interaction between epithelial and the surrounding mesenchyme. The failure of this interaction results in severe developmental birth defects such as tracheo-esophageal fistula. In this study, we separately generated respiratory and esophageal mesenchyme from human pluripotent stem cells by mimicking the process of normal organogenesis. Furthermore, these cells were combined to establish more complex organ-like structure. In the organoids, we observed signaling interaction between epithelial cells and the surrounding mesenchymal cells. This technique can be applied for the study of normal human organogenesis and disease modeling.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、間充織細胞を豊富に含む呼吸器並びに食道オルガノイドをヒトES細胞から作成する儀実基盤を確立することができた。本研究成果は、ヒト臓器の正常発生を研究するモデルとして有用なツールとしての活用が期待される。さらに、これらのオルガノイドにおいて、呼吸器・食道疾患に起因する遺伝子を操作することによって、病態を培養皿上で再現するモデルとして期待される。