Tissue size control with synthetic cell-cell signaling

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15828
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44040:Morphology and anatomical structure-related
• Research Institution: Kanazawa University
• Principal Investigator: Toda Satoshi 金沢大学, ナノ生命科学研究所, 助教 (20738835)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 合成生物学 / 細胞間コミュニケーション / モルフォゲン / パターン形成 / 細胞増殖

Outline of Final Research Achievements

To test how cell-cell communications generate and maintain multicellular structures, we constructed an original model system where green fluorescent protein (GFP) works as an artificial intercellular signaling molecule. In this system, a cell secretes GFP and another cell binds secreted GFP to the cell surface with a synthetic receptor to induce target gene expression. By introducing this system into cultured cells, we artificially reconstructed a signal gradient formation in the population of GFP-receiving cells, suggesting that we successfully made GFP function like a morphogen, a diffusible cell-cell signaling molecule. Using this synthetic morphogen model, we explored the basic principles to regulate multicellular dynamics by manipulating model parameters such as an expression level of synthetic receptors and cellular responses such as feedback circuits and cell proliferation.

Free Research Field

合成生物学

Academic Significance and Societal Importance of the Research Achievements

生体組織内におけるシグナル分子の分布や個々の細胞の状態をすべて把握することは困難であるため、本研究では、培養皿上でシグナル分子が細胞動態を制御する仕組みそのものを再構成し、細胞集団が自律的に多細胞組織を形成・維持する原理を解析した。細胞間シグナルを人工構築する技術は、細胞の分化を空間的に制御して人工組織を構築する組織工学分野や、体内の必要な場所へ細胞を送り込む細胞医薬開発への応用が期待される。