Maintenance of undifferentiated state and cell fate tracing by visualization of mesenchymal stem cells in vivo

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05173
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Shimane University
• Principal Investigator: Matsuzaki Yumi 島根大学, 学術研究院医学・看護学系, 教授 (50338183)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 間葉系幹細胞 / 未分化性維持 / Wntシグナル / Notchシグナル / レポーター遺伝子 / 体内動態

Outline of Final Research Achievements

By systematically elucidating the molecular mechanism in determining the undifferentiated maintenance of MSC and determining the direction of differentiation in this study, the mechanism to control the undifferentiated maintenance of stem cells / progenitor cells / mature cells and the directionality of differentiation is inscribed. An attempt was made to understand both in vivo and in vitro. As a result, FZD5 suppresses cellular senescence by activating the non-classical pathway by forced expression and knockdown of FZD5 and Notch2, and that Notch2 is upregulated under hypoxic conditions and induces cell proliferation It became clear. Furthermore, we generated a reporter transgenic mouse using MSC specific gene expression regulatory region and clarified that its expression is localized to undifferentiated MSC.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

多くのMSC研究は培養MSC又は不死化した細胞株を用いた実験に頼らざるを得ず、得られた結果が真にMSCの性状を反映したものかは不明であった。また、生体内での性状解析もほとんど解析されて来なかった。本研究では、高純度のヒトMSC(REC)を用いて未分化性維持機構の解析を行った。さらに、独自に開発したレポーターマウスを用いて、MSCからの間質細胞への細胞系譜の可視化と動態の解析を行った。これらのアプローチは、個々の細胞が持つ性質を解析する上で生理的条件に最も近く、間葉細胞系譜の生理機能を本質的に理解するには必要かつ適切であり、学術的ばかりでなく、安全な先進医療を確立する上でも大きな意義を持つ。