Study on the molecular basis that defines organ regenerative ability in an anuran amphibian (Xenopus laevis)

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K21517
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Kubo Takeo 東京大学, 大学院理学系研究科(理学部), 教授 (10201469)
• Project Period (FY): 2020-07-30 – 2024-03-31
• Keywords: アフリカツメガエル / 器官再生 / 再生芽 / Single cell RNA-seq / Crispr/Cas9 / Side population法 / IL-11 / マクロファージ

Outline of Final Research Achievements

We analyzed the molecular basis and cellular dynamics to explore the molecular factors determining organ regenerative ability in Xenopus laevis tadpoles. In this research period, (1) We identified the steap4+ cell population as a candidate cell population associated with enhanced morphogenesis by FGF10 after tadpole limb bud amputation. (2) We identified immune cells able to promote larval tail regeneration and a gene essential for their function. (3) We previously showed that il11 is essential in tadpole tail regeneration. Here we showed that its receptor is also important for tail regeneration. (4) We first established and improved a knock-in method in X. laevis. (5) We established a method for enrichment and fractionation of tissue stem cells of regenerating tadpole tails by side-population method. The results of each research subject were published in international journals.

Free Research Field

Regenerative biology

Academic Significance and Societal Importance of the Research Achievements

動物の器官再生能に関する研究は、基礎生物学のみならず、将来的には臨床応用の観点からも重要である。本研究課題の最終目標は、両生類のもつ高い器官再生能を支える両生類固有な分子基盤・細胞挙動を解明することである。本研究課題ではアフリカツメガエル幼生の肢芽切断後の形態の再形成に関与する新規な候補細胞集団の同定、尾再生に必須な新規遺伝子の同定に加えて、幼生尾再生芽からの組織幹細胞濃縮分画の単離法や、ツメガエルゲノムの任意部位へのノックイン法の確立と改善と言う、将来的な研究発展の礎となる研究基盤を整備した。これらの研究成果は何れも独自性が高く、再生生物学分野において重要な貢献をなすものと考えている。