Molecular mechanism for the acquisition of multipotency by ribosome

• Project/Area Number: 18K19344
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: Kumamoto University
• Principal Investigator: OHTA KUNIMASA 熊本大学, 大学院生命科学研究部(医), 准教授 (90244128)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: リボソーム / 多能性獲得 / リプログラミング / ヒト癌細胞

Outline of Final Research Achievements

We tried to elucidate the molecular mechanism of cellular reprogramming byribosome. We found that ribosome was incorporated into cells by endocytosis and trypsin treatment. We also found that one of ribosome proteins have a cell cluster formation activity. When we addedribosome into the human cancer cell after trypsin treatment, some human cancer cells formed cellcluster and stopped their cell proliferation.

Academic Significance and Societal Importance of the Research Achievements

正常細胞にリボソームを取り込ませると、細胞塊を形成し、増殖が停止する。ヒト癌細胞（肺癌、乳癌、大腸癌、肝臓癌）でさえ大腸菌由来リボソームを取り込むと、細胞塊を形成し、その増殖が完全に抑えられることをシャーレ内で見出している。今後は、正常細胞を用いた研究で得られた実験結果を、ヒト癌細胞にも応用することにより、ヒト癌細胞の細胞周期制御機構や細胞増殖停止機構を明らかに出来、将来の安全・安心な抗がん剤の開発に発展する可能性がある。

Research Products

• [Journal Article] Akhirin regulates the proliferation and differentiation of neural stem cells/progenitor cells at neurogenic niches in mouse brain. (2020)
  • Author(s): Anam MB, Ahmad SAi, Kudo M, lstiaq A, Felemban AAM, Ito N, Ohta K.
  • Journal Title: Dev Growth Differ Volume: 62(2) Issue: 2 Pages: 97-107
  • DOI: 10.1111/dgd.12646
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tsukushi is essential for proper maintenance and terminal differentiation of mouse hippocampal neural stem cells. (2020)
  • Author(s): Ahmad SAi, Anam MB, lstiaq A, Ito N, Ohta K.
  • Journal Title: Dev Growth Differ Volume: 62(2) Issue: 2 Pages: 108-117
  • DOI: 10.1111/dgd.12649
  • Peer Reviewed
• [Journal Article] Tsukushi is essential for the development of the inner ear (2020)
  • Author(s): Miwa Toru、Ohta Kunimasa、Ito Naofumi、Hattori Satoko、Miyakawa Tsuyoshi、Takeo Toru、Nakagata Naomi、Song Wen-Jie、Minoda Ryosei
  • Journal Title: Molecular Brain Volume: 13 Issue: 1 Pages: 29-29
  • DOI: 10.1186/s13041-020-00570-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Significance of Tsukushi in lung cancer. (2019)
  • Author(s): Yamada T, Ohta K, Motooka Y, Fujino K, Kudoh S, Tenjin Y, Sato Y, Matsuo A, Ikeda K Suzuki M, Ito T.
  • Journal Title: Lung Cancer Volume: 131 Pages: 104-111
  • Peer Reviewed
• [Journal Article] The hepatokine Tsukushi gates energy expenditure via brown fat sympathetic innervation (2019)
  • Author(s): Wang, Q., Sharma, V.P., Shen, H., Xiao, Y., Zhu, Q., Xiong, X., Guo, L., Jiang, L., Ohta, K., Li, S., Shi, H., Rui, L., and Lin, J.D
  • Journal Title: Nature Metabolism Volume: 1 Pages: 251-260
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CCN2/CTGF binds the small leucine rich proteoglycan protein Tsukushi (2019)
  • Author(s): Ohta K., Aoyama E., Ahmad SAI, Ito N., Anam MB, Kubota S. and Takigawa M
  • Journal Title: Journal of Cell Communication and Signaling Volume: 13(1) Issue: 1 Pages: 113-118
  • DOI: 10.1007/s12079-018-0487-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transdifferentiation of human somatic cells by ribosome (2018)
  • Author(s): Naofumi Ito, Mohammad Badrul Anam, Ahmad Shah Adil Ishtiyaq , Kunimasa Ohta.
  • Journal Title: Development Growth and Differentiation Volume: 60(5) Issue: 5 Pages: 241-247
  • DOI: 10.1111/dgd.12538
  • Peer Reviewed / Open Access
• [Presentation] Mammalian cells acquire cellular lineage plasticity by incorporating ribosomes (2019)
  • Author(s): 伊藤 尚文、太田 訓正
  • Organizer: 第52回日本発生生物学会
• [Presentation] Transdifferentiation of human somatic cells by ribosome (2019)
  • Author(s): 太田 訓正
  • Organizer: 第17回幹細胞シンポジウム
• [Presentation] Transdifferentiation of human somatic cells by ribosome (2019)
  • Author(s): 太田 訓正
  • Organizer: 第11回日本CCNファミリー研究会.
• [Presentation] 乳酸菌による細胞の形質転換機構 (2019)
  • Author(s): 太田 訓正
  • Organizer: 第 72 回 日本細菌学会九州支部総会 第 56 回 日本ウイルス学会九州支部総
• [Presentation] Transdifferentiation of human somatic cells by ribosomeTransdifferentiation of human somatic cells by ribosome (2019)
  • Author(s): 太田 訓正
  • Organizer: 第42回日本分子生物学会
• [Presentation] Transdifferenciation of human cancer cells by ribosome (2019)
  • Author(s): 工藤 三希子、太田 訓正
  • Organizer: 第42回日本分子生物学会
• [Presentation] Incorporation of Bacterial Ribosome in Mouse Enteroid and Further Implications (2019)
  • Author(s): Arif, I., Urata, K.、太田 訓正
  • Organizer: 第42回日本分子生物学会
• [Presentation] Lactic Acid Bacteria Converts Human Fibroblasts to Multipotent cells. (2019)
  • Author(s): 太田 訓正
  • Organizer: Kumamoto - NCBS/InStem Partnership Meeting.
  • Int'l Joint Research / Invited
• [Presentation] EquarinはFGFシグナルを制御して水晶体形成に関与する (2018)
  • Author(s): 太田 訓正
  • Organizer: 第１２２回 日本眼科学会総会（招待講演）
• [Presentation] Disruption of Tsukushi function leads to the hydrocephalus by aberrant neurogenesis in the brain (2018)
  • Author(s): 太田 訓正
  • Organizer: 第22回国際神経発生生物学会
  • Int'l Joint Research
• [Presentation] Ribosome incorporation into somatic cells promotes reprogramming towards multipotent cells (2018)
  • Author(s): 太田 訓正
  • Organizer: 第16回 幹細胞シンポジウム
• [Presentation] Ribosomes convert human fibroblasts to multipotent cells. (2018)
  • Author(s): 太田 訓正
  • Organizer: 第70回日本細胞生物学会・第51回日本発生生物学会合同大会学会
• [Presentation] Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency (2018)
  • Author(s): 太田 訓正
  • Organizer: 第8回オルソオルガノジェネシス検討会
• [Presentation] リボソームによる細胞のリプログラミング機構 (2018)
  • Author(s): 太田 訓正
  • Organizer: 第577回 難研セミナー 第150回 難治疾患共同研究拠点セミナー 第 1 回 RCC イメージングユニットセミナー
  • Invited
• [Presentation] Tsukushiと突発性正常圧水頭症の関連 (2018)
  • Author(s): 太田 訓正
  • Organizer: 第10回日本CCNファミリー研究会
• [Presentation] Transdifferentiation of human somatic cells by ribosome (2018)
  • Author(s): 太田 訓正
  • Organizer: 第 5 回 Ribosome Meeting.
• [Presentation] Tsukushiを介した神経幹細胞ニッチ制御と水頭症の連関. (2018)
  • Author(s): 太田 訓正
  • Organizer: 2018年度生理学研究所研究会「神経発達・再生研究会」
• [Presentation] DISRUPTION OF TSUKUSHI FUNCTION LEADS TO THE HYDROCEPHALUS BY ABERRANT NEUROGENESIS IN THE BRAIN (2018)
  • Author(s): 太田 訓正
  • Organizer: Hydrocephalus Meeting 2018
  • Invited
• [Book] 毛髪科学の新展開 監修： 岩渕徳郎 毛周期調節におけるTsukushi とTGF-βシグナル (2019)
  • Author(s): 工藤三希子、伊藤尚文、河野利恵、太田訓正
  • Publisher: シーエムシー出版
  • ISBN: 9784781314341
• [Remarks] 熊本大学 大学院生命科学研究部 神経分化学分野
  • URL: http://srv02.medic.kumamoto-u.ac.jp/dept/devneuro/index.html
• [Remarks] 熊本大学 大学院生命科学研究部 神経分化学教室
  • URL: http://srv02.medic.kumamoto-u.ac.jp/dept/devneuro/