Clarification of the cell-quality-control systems eliminating unhealthy cells from embryonic tissue and their dysregulation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21502
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Osaka University
• Principal Investigator: Ishitani Tohru 大阪大学, 微生物病研究所, 教授 (40448428)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: モザイク疾患 / 不良細胞

Outline of Final Research Achievements

We aimed to elucidate the relationship between mosaic disease and cell-quality-control system using zebrafish as a model. We succeeded to reveal that, in zebrafish larvae, neighboring normal cells sense precancerous cells and then induce senescence and physically push out these precancerous cells. In addition, in epithelia with p53 mutations or DNA damage, precancerous cells survive without being eliminated, and induce proliferation or secondary cellular senescence in adjacent normal cells to induce primary tumors.Thus,
we have clarified a new mechanism by which neighboring cells sense and eliminate defective cells during development. Furthermore, we have clarified that additional mutations and environmental factors suppress this elimination mechanism and drive disease development. Our results would provide a new understanding of the pathogenesis of human diseases.

Free Research Field

発生細胞生物学

Academic Significance and Societal Importance of the Research Achievements

ゼブラフィッシュを用いたイメージング解析により、新たな疾患発症機構を明らかにした。これは、発生学のみならず医学においても重要な発見である。また、近年、動物愛護の考え方から哺乳類モデルを使った制限が徐々に制限され始めているが、本成果は非哺乳類モデルの医学研究における有用性を示す重要な成果と言える。