Molecular mechanism for the acquisition of multipotency by ribosome

• Project/Area Number: 16H04795
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• 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)
• Co-Investigator(Kenkyū-buntansha): 高橋 淑子 京都大学, 理学研究科, 教授 (10183857)
• Research Collaborator: ITO naofumi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: リボゾーム / 多能性獲得 / リプログラミング / ヒト癌細胞 / リボソーム

Outline of Final Research Achievements

We tried to elucidate the molecular mechanism of cellular reprogramming by ribosome. 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 added ribosome into the human cancer cell after trypsin treatment, some human cancer cells formed cell cluster 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] 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
• [Journal Article] Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency (2018)
  • Author(s): Ito Naofumi、Katoh Kaoru、Kushige Hiroko、Saito Yutaka、Umemoto Terumasa、Matsuzaki Yu、Kiyonari Hiroshi、Kobayashi Daiki、Soga Minami、Era Takumi、Araki Norie、Furuta Yasuhide、Suda Toshio、Kida Yasuyuki、Ohta Kunimasa
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1634-1634
  • DOI: 10.1038/s41598-018-20057-1
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of Tsukushi in diverse developmental processes. (2018)
  • Author(s): Shah A., I., A., Mohammad B., A., Ito I., and Ohta K.
  • Journal Title: Joural of Cell Communication and Signaling Volume: 12(1) Issue: 1 Pages: 205-210
  • DOI: 10.1007/s12079-018-0452-8
  • Peer Reviewed / Open Access
• [Presentation] Lactic Acid Bacteria Converts Human Fibroblasts to Multipotent cells (2019)
  • Author(s): 太田 訓正2019
  • 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
  • Invited
• [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
• [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
  • Invited
• [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
  • Int'l Joint Research
• [Presentation] 神経幹細胞ニッチを制御するTsukushiと水頭症の連関 (2018)
  • Author(s): 太田訓正
  • Organizer: 第17回日本再生医療学会総会.
• [Presentation] Ribosome converts human fibroblasts to multipoint cells (2018)
  • Author(s): 太田訓正
  • Organizer: 国際ミニシンポジウム「Frontline in Developmental Biology」学会大会
  • Int'l Joint Research / Invited
• [Presentation] Ribosome converts human fibroblasts to multipoint cells (2018)
  • Author(s): 太田 訓正
  • Organizer: 国際ミニシンポジウム「Frontline in Developmental Biology」学会大会
  • Int'l Joint Research / Invited
• [Presentation] Ribosome incorporation into somatic cells promotes lineage transdifferentiation towards multipotency (2018)
  • Author(s): Naofumi Ito, Shah Adil Ishtiyaq Ahmad, Mohammad Badrul Anam, Kunimasa Ohta
  • Organizer: The program released_JSPS & NUS Joint 2nd Symposium 2018
• [Presentation] Ribosome incorporation into somatic cells promotes lineage transdifferentiation towards multipotency (2018)
  • Author(s): Naofumi Ito, Shah Adil Ishtiyaq Ahmad, Mohammad Badrul Anam, Kunimasa Ohta.
  • Organizer: KEY Forum 2018 Stem Cell Traits and Developmental Systems
• [Presentation] Ribosome incorporation into somatic cells promotes lineage transdifferentiation towards multipotency (2018)
  • Author(s): Naofumi Ito, Shah Adil Ishtiyaq Ahmad, Mohammad Badrul Anam, Kunimasa Ohta
  • Organizer: 第4回 包括的神経グリア研究会 UNG light 2018
• [Presentation] Ribosome incorporation into somatic cells promotes reprogramming towards multipotent cells (2018)
  • Author(s): Kunimasa Ohta, Adil Ishtiyaaq, Naofumi Ito
  • Organizer: 第50回 日本発生生物学会年会
• [Presentation] 水晶体形成時におけるEquarinの機能解析 (2017)
  • Author(s): 太田訓正
  • Organizer: 第121回日本眼科学会総会
  • Invited
• [Presentation] Ribosome incorporation into somatic cells promotes reprogramming towards multipotent cells (2017)
  • Author(s): 太田訓正
  • Organizer: 第50回 日本発生生物学会年会
• [Presentation] Tsukushi dysfunction leads to hydrocephalus by altering neurogenesis in the subventricular zone (2017)
  • Author(s): 太田訓正
  • Organizer: 第15回 幹細胞シンポジウム
• [Presentation] Dysfunction of Tsukushi leads to hydrocephalus by altering neurogenesis in the subventricular zone (2017)
  • Author(s): 太田訓正
  • Organizer: Summer Retreat 2017
• [Presentation] Dysfunction of Tsukushi, a soluble molecule belonging to the small leucine-rich proteoglycan family, leads to hydrocephalus by altering neurogenesis in the brain (2017)
  • Author(s): 太田訓正
  • Organizer: 第９回日本CCNファミリー研究会
• [Presentation] Ribosome incorporation into somatic cells promotes reprogramming towards multipotencytowards multipotency (2017)
  • Author(s): 太田訓正
  • Organizer: 国立遺伝子研究所セミナー
• [Presentation] Lactic acid bacteria convert human fibroblasts into multipotent cells (2017)
  • Author(s): 太田訓正
  • Organizer: 6th BENEFICIAL MICROBES CONFERENCE 2017.
  • Int'l Joint Research / Invited
• [Presentation] Dysfunction of Tsukushi, a soluble molecule belonging to the small leucine-rich proteoglycan family, leads to hydrocephalus by altering neurogenesis in the brain. (2017)
  • Author(s): 太田訓正
  • Organizer: The 9th INTERNATIONAL WORKSHOP ON THE CCN FAMILY OF GENES.
  • Int'l Joint Research / Invited
• [Presentation] Tsukushi の機能不全によりニッチ制御が乱れ、水頭症が発症する (2017)
  • Author(s): 太田訓正
  • Organizer: 第 13 回成体脳のニューロン新生懇談会
• [Presentation] Dysfunction of Tsukushi, a soluble molecule belonging to the small leucine-rich proteoglycan family, leads to hydrocephalus by altering neurogenesis in the brain (2017)
  • Author(s): 太田訓正
  • Organizer: 第13回日中交流国際生命科学シンポジウム
  • Int'l Joint Research / Invited
• [Presentation] リボソーム取り込みによるヒト細胞の多能性獲得 (2017)
  • Author(s): 伊藤尚文、Shah Adil Ishtiyaq Ahmad、Mohammad Badrul Anam、太田訓正
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Lactic acid bacteria convert human fibroblasts into multipotent cells (2017)
  • Author(s): Kunimasa Ohta
  • Organizer: 6th BENEFICIAL MICROBES CONFERENCE 2017
  • Int'l Joint Research / Invited
• [Presentation] Ribosome incorporation into somatic cells promotes reprogramming towards multipotency (2017)
  • Author(s): Kunimasa Ohta
  • Organizer: 国立遺伝子研究所セミナー
  • Invited
• [Presentation] 微生物由来多能性誘導因子による細胞運命の転換 (2017)
  • Author(s): 伊藤 尚文、太田訓正
  • Organizer: 第7回オルソオルガノジェネシス検討会
• [Book] 乳酸菌による細胞リプログラミング (2018)
  • Author(s): 伊藤尚文、太田訓正
  • Total Pages: 264
  • Publisher: シーエムシー出版
  • ISBN: 9784781313177
• [Book] Cell reprogramming by Lactic Acid Bacteria (2018)
  • Author(s): Ito N., and Ohta K
  • Publisher: Applied RNA Biosciences. (Eds. Matsuda S. and Izawa S.)
• [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/
• [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/