Intrinsic-, extrinsic factors for long-term maintenance of planarian stem cells

• Project/Area Number: 17K07421
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Tsuyama National College of Technology
• Principal Investigator: Shibata Norito 津山工業高等専門学校, 総合理工学科, 准教授 (60402781)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 幹細胞 / プラナリア / 全能性 / ニッチ / 全能性幹細胞 / MTA / 細胞移動 / 再生

Outline of Final Research Achievements

Planarian has regenerative ability which planarian can regenerate from almost all tiny body fragments. We maintain planarians only by regeneration for 29 years in our laboratory. This remarkable regenerative ability is dependent on pluripotent stem cells called neoblasts. In this study, I focused on how planarian can maintain neoblasts for a long time. In the result, I found that planarian MTA genes might be involved in maintenance of neoblasts. When I inhibited gene function of planarian MTA by RNAi, planarian could not regenerate even though neoblasts existed. This result suggests that MTA-depleted neoblast can not differentiate into several differentiated cells. Thus, MTA might regulate precise cell differentiation from neoblasts, and maintenance of neoblasts.

Academic Significance and Societal Importance of the Research Achievements

あらゆる細胞種になれる万能細胞であるES細胞の元になる哺乳類の内部細胞塊は発生過程のごく初期に一過的に現れるが、発生過程が進むと万能性を持つ細胞は失われる。一方で、プラナリアは大人になっても多くの万能細胞である新生細胞を身体中に維持して、がん化させることなく自由自在に操っている。ES細胞を成体内で維持する機構がない哺乳類では、長期にわたる万能幹細胞の維持のメカニズムを知ることはできない。今回、プラナリアというユニークな生物を使うことで、哺乳類ではガンの転移の際に働くことが知られているMTA遺伝子が万能細胞の維持、移動、分化に関与しているらしいことを明らかにできた。

Research Products

• [Journal Article] Searching for non-transposable targets of planarian nuclear PIWI in pluripotent stem cells and differentiated cells (2018)
  • Author(s): Makoto Kashima, Kiyokazu Agata, Norito Shibata
  • Journal Title: Develop. Growth Differ. Volume: 4 Issue: 5 Pages: 1-18
  • DOI: 10.1111/dgd.12536
  • Peer Reviewed
• [Journal Article] RNA Interference in Planarians: Feeding and Injection of Synthetic dsRNA. (2018)
  • Author(s): Norito Shibata, Kiyokazu Agata
  • Journal Title: Methods Mol. Biol. Volume: 1774 Pages: 455-466
  • DOI: 10.1007/978-1-4939-7802-1_18
  • ISBN: 9781493978007, 9781493978021
• [Presentation] 再生シグナルに応答したプラナリア幹細胞の活性化 (2019)
  • Author(s): 柴田 典人
  • Organizer: 日本動物学会第90回大会
  • Invited
• [Presentation] Heterogeneity of RNP granules specific to planarian adult pluripotent stem cells and its functions (2018)
  • Author(s): Kumagai, N., Kashima., M, Shibata, N., Agata, K.
  • Organizer: International Planarian Meeting
  • Int'l Joint Research
• [Presentation] The migration of neoblasts in Dugesia japonica, indicating the different stem cell regulation within highly regenerative planarians (2018)
  • Author(s): Sato, Y., Shibata, N., Agata, K.
  • Organizer: International Planarian Meeting
  • Int'l Joint Research
• [Presentation] 成体多能性幹細胞に特異的なRNP顆粒の不均一性とその機能 (2018)
  • Author(s): 熊谷信是、鹿島誠、柴田典人、阿形清和
  • Organizer: 日本動物学会 第89回大会
• [Presentation] プラナリア種間における異なる全能性幹細胞の移動制御機構 (2018)
  • Author(s): 佐藤勇輝、柴田典人、阿形清和
  • Organizer: 日本動物学会 第89回大会
• [Presentation] New categorization of planarian stem cell population based on possible stem cell niche (2017)
  • Author(s): Sato, Y. Shibata, N. and Agata, K
  • Organizer: 日本発生生物学会第50回大会
• [Presentation] プラナリアの胚発生期における全能性幹細胞ニッチの形成 (2017)
  • Author(s): Sato, Y. Nagao, R. Shimazaki, A. Sekii, K. Kobayashi, K. Shibata, N. and KAgata, K
  • Organizer: 日本動物学会第87回大会
• [Presentation] プラナリアの幹細胞を起点とする前後軸に沿った再生の分子機構 (2017)
  • Author(s): 柴田典人
  • Organizer: 平成29年度中国四国地区生物系三学会合同大会