Molecular mechanisms on the cellular response induced by organella damages

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07507
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Intoh Atsushi 奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (70779058)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 幹細胞制御 / オルガノイド / iPS細胞 / 疾患発症機序 / オルガネラ / バイオマーカー / 細胞膜タンパク質

Outline of Final Research Achievements

In this study, we first generated human iPSC-derived mesodermal elongation model to elucidate cellular responses by environmental materials. We also treated the elongation tissues with placental permeability chemicals and found that some toxic compounds induced inhibition of the elongation, which is caused by disturbance of WNT signaling (Ninomiya H et al, Chemosphere, 2020).
Additionally, we established human iPSC-derived gastric organoids with mature cell compositions. We are creating gastric cancer models from this organoid system, and elucidating disturbance of gene expression among tumorigenesis and gastric ulcer. In relation to this examination, we also identified a novel plasma membrane protein that is significantly downregulated by extracellular stimuli. We expected this protein can be a cell surface marker for tumorigenesis and also as a functional protein that regulates stemness and tissue homeostasis.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で行ったオルガノイドを用いた疾患モデル解析の成果は、創薬スクリーニングや早期診断のバイオマーカーの同定に有用であると期待される。これまでは動物実験や単一細胞種における解析が主だった疾患機序の解明手法に加えて、複雑な細胞群が構成する立体構造を持った機能的なオルガノイドを用いた疾患モデルの樹立を行うことで、疾患発症機序のより深い理解に繋がるものである。今後の詳細な解析を経ることでスクリーニングツールとしての実用化を目指す。