Molecular mechanisms underlying the age-related changes in the stem cell competency

• Project/Area Number: 24689017
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kaneda Hayato 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 上級研究員 (40528212)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000); Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2012: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 幹細胞老化 / microRNA / 間葉系幹細胞 / 老化 / 組織幹細胞 / 幹細胞 / 分化 / 再生医学 / シグナル伝達

Outline of Final Research Achievements

We revealed the molecular mechanisms underlying the competence regulation in neural stem/progenitor cells. A certain microRNA is a key regulator for it and this regulatory system is necessary for spatio-temporally specific proper responses to the cell-extrinsic signals (Naka-Kaneda H. et al. PNAS, 2014). This system is also important for the aging of mesenchymal stem/stromal cells (MSCs) and associated with the decline in differentiation potential and expression of secretory factors. We identified a regenerative factor-derived from MSCs for age-related disorders. Upregulation of the factor ameliorates reduction of lymphocytes, insufficient muscle repair capacity, decrease of neural progenitors, and chronic inflammation.

Research Products

• [Journal Article] 神経幹細胞の時系列的な分化能の変化とそのメカニズム (2015)
  • Author(s): 金田勇人、島崎琢也、岡野栄之
  • Journal Title: 実験医学 (増刊) Volume: 33 Pages: 121-126
• [Journal Article] MicroRNA-mediated regulation of the neurogenic-to-gliogenic competence transition of neural stem/progenitor cells (2014)
  • Author(s): Naka-Kaneda H, Shimazaki T & Okano H
  • Journal Title: Neurogenesis Volume: 1 Issue: 1 Pages: e29542-e29542
  • DOI: 10.4161/neur.29542
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The miR-17/106-p38 axis is a key regulator of the neurogenic-to-gliogenic transition in developing neural stem/progenitor cells (2014)
  • Author(s): Hayato Naka-Kanedaa, Shiho Nakamuraa, Mana Igarashi, Hisashi Aoid, Hiroaki K ankib, Jun Tsuyama, Shuichi Tsutsumie, Hiroyuki Aburatanie, Takuya Shimazakib, and Hideyuki Okano.
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 111(4) Issue: 4 Pages: 1604-1609
  • DOI: 10.1073/pnas.1315567111
  • Peer Reviewed
• [Presentation] microRNAによる幹細胞老化の制御と組織恒常性の回復 (2015)
  • Author(s): 金田勇人
  • Organizer: SKIPセミナー
  • Place of Presentation: 東京
  • Year and Date: 2015-12-11
  • Invited
• [Presentation] 間葉系幹細胞が分泌する恒常性維持因子の探索と機能解析 (2015)
  • Author(s): 金田 勇人
  • Organizer: 日本再生医療学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-03-19 – 2015-03-21
• [Presentation] 幹細胞老化のメカニズムと制御 (2015)
  • Author(s): 金田 勇人
  • Organizer: 日本再生医療学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-03-19 – 2015-03-21
  • Invited
• [Presentation] 組織幹細胞に共通する老化メカニズムの解析 (2014)
  • Author(s): 金田（仲） 勇人、大石（太野） 路子、中村 志穂、馬渕 洋
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 組織幹細胞に共通する老化メカニズムの解析と制御法の開発 (2014)
  • Author(s): Kaneda H, Mabuchi Y, Oishi M, Nakamura S, Yamaji T, Matsuzaki Y, Shimazaki T, Okano H.
  • Organizer: 日本再生医療学会
  • Place of Presentation: 京都府、国際会館
• [Presentation] What is the aging? (2013)
  • Author(s): Kaneda H
  • Organizer: Society for Young Stem Cell Researchers
  • Place of Presentation: 東京都、先端生命医科学センター TWIns
  • Invited
• [Presentation] Functional Restoration of Aged Stem Cells by Regulating Their Competence. (2013)
  • Author(s): Naka-Kaneda H, Ohno-Oishi M, Mabuchi Y, Nakamura S.
  • Organizer: 幹細胞シンポジウム
  • Place of Presentation: 東京都、東京大学 伊藤国際学術研究センター
• [Presentation] Bidirectional Control of Neural Stem Cell Competence (2012)
  • Author(s): 金田 勇人
  • Organizer: 日本分子生物学会
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2012-12-14
• [Presentation] Bidirectional Control of Neural Stem Cell Competence (2012)
  • Author(s): 金田 勇人
  • Organizer: 日本神経科学学会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2012-09-19
• [Presentation] BIDIRECTIONAL CONTROL OF THE COMPETENCE OF MOUSE AND HUMAN NEURAL STEM CELLS (2012)
  • Author(s): 金田 勇人
  • Organizer: International Society for Stem Cell Research
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2012-06-14
• [Presentation] BIDIRECTIONAL CONTROL OF COMPETENCE IN MOUSE AND HUMAN NEURAL STEM CELLS (2012)
  • Author(s): 金田 勇人
  • Organizer: 幹細胞シンポジウム
  • Place of Presentation: 淡路夢舞台国際会議場(兵庫県)
  • Year and Date: 2012-05-31
• [Book] 実験医学増刊 (2015)
  • Author(s): 金田 勇人, 島崎 琢也, 岡野 栄之
  • Total Pages: 238
  • Publisher: 羊土社
• [Book] 日本臨牀 (2015)
  • Author(s): 金田 勇人, 島崎 琢也, 岡野 栄之
  • Total Pages: 583
  • Publisher: 日本臨牀社
• [Patent(Industrial Property Rights)] 加齢による生理機能の低下を回復または改善する組成物 (2015)
  • Inventor(s): 金田勇人
  • Industrial Property Rights Holder: 国立研究開発法人理化学研究所
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-256045
  • Filing Date: 2015-12-28
• [Patent(Industrial Property Rights)] 神経分化促進剤 (2013)
  • Inventor(s): 岡野栄之、島崎琢也、仲勇人
  • Industrial Property Rights Holder: 岡野栄之、島崎琢也、仲勇人
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-04-26
  • Acquisition Date: 2015-08-21
• [Patent(Industrial Property Rights)] 神経分化促進剤 (2012)
  • Inventor(s): 金田勇人, 岡野栄之, 島崎琢也
  • Industrial Property Rights Holder: 学校法人慶應義塾, 独立行政法人理化学研究所
  • Industrial Property Number: 2012-103875
  • Filing Date: 2012-04-27