Functional elucidation of TWIST 1 in stemness of Mesenchymal stem cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18937
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: Kindai University
• Principal Investigator: MORI Tatsufumi 近畿大学, ライフサイエンス研究所, 助手 (40760492)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 間葉系幹細胞 / 転写因子

Outline of Final Research Achievements

MSCs are somatic stem cells can isolated from various connective tissues such as bone marrow, fat, and synovial membrane. Because of its properties of cytokine secretion, multiple differentiation and niche formation, MSCs has been an attractive cell source for cell transplantation therapy. On the other hand, molecular mechanisms regulating stemness of the MSCs is largely unknown. Here we focused on a transcription factor TWIST1 as a molecule involving stemness of the MSCs. In the human MSCs, overexpression of TWIST1 significantly activated cell proliferation and inhibited differentiation, contrary, suppression of TWIST1 resulted in reduction of cell proliferation. Transcriptome and ChIPseq analysis revealed that TWIST1 directly bind to promoter region of other transcription factors regulating undifferentiation status of the stem cells. From these we concluded that TWIST1 is a master regulator of stemness in the MSCs and useful as a marker evaluating potentials of the MSCs.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

MSCにおける重要な転写因子が明らかとなることで、新しい再生医療技術の開発や移植用細胞の評価法の開発につながる。また、TWIST1は骨肉腫など間葉系の癌で高発現となることが報告されており、TWIST1の制御技術を研究することで新しい癌治療の開発にもつながる。