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Differentiation of human iPS cells by CCN

Research Project

Project/Area Number 18K06645
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionTokushima Bunri University

Principal Investigator

Kuzuhara Takashi  徳島文理大学, 薬学部, 教授 (00260513)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsジアジフェノライド / ヒトiPS細胞 / 神経前駆細胞 / CCN / CCN2 / 神経突起伸展 / p-44/42 MAP / リン酸化 / 骨芽細胞 / iPS細胞 / 神経栄養因子 / バングル / 神経栄養因子様活性 / p44/42 MAPK / 神経分化 / 骨形成因子 / iPS
Outline of Final Research Achievements

Comprehensive RNA sequencing showed that mRNA level expression of smooth muscle protein 22-alpha (SM22a), annexin A2 (ANXA2), CCN2, IGFBP3, and CCN1 were up-regulated, whereas those of the TP53 was down-regulated by treatment with jiadifenolide. In silico molecular network analysis showed that the up-regulated mRNA level expression of CCN, CCN1, CCN2, SM22a, ANXA2, and IGFBP3 genes were related to the regulation of SMAD, SMAD1, SMAD2, SMAD3, nuclear factor-κB (NF-κB), and STAT3 or p53. RT-qPCR showed that expression levels of CCN1, CCN2, CCN6, SM22a, and AXNA2 mRNA were significantly up-regulated in jiadifenolide-treated cells. These results showed that jiadifenolide activates CCN signaling via up-regulating the mRNA level expression of the CCN family members CCN1, CCN2, and CCN6, and CCN2 gene expression. CCN2 protein promoted neuronal dendritic outgrowth and increased neuronal cell numbers and increased phosphorylation of p44/42 MAPK protein in human neuronal precursor cells.

Academic Significance and Societal Importance of the Research Achievements

骨形成因子CCNファミリータンパク質が神経分化に関与するという研究は他には全く無く世界の中でも極めて創造性が高い研究と言える。この研究を通して、神経細胞の分化と骨形成の接点が明らかになる可能性がある。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (30 results)

All 2021 2020 2019 2018 Other

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 8 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Acetylation of the influenza A virus polymerase subunit PA in the N‐terminal domain positively regulates its endonuclease activity2021

    • Author(s)
      Hatakeyama Dai、Shoji Masaki、Ogata Seiryo、Masuda Takeshi、Nakano Masahiro、Komatsu Tsugunori、Saitoh Ayaka、Makiyama Kyoko、Tsuneishi Hazuki、Miyatake Asuka、Takahira Mizuki、Nishikawa Erina、Ohkubo Ayana、Noda Takeshi、Kawaoka Yoshihiro、Ohtsuki Sumio、Kuzuhara Takashi
    • Journal Title

      The FEBS Journal

      Volume: 289 Issue: 1 Pages: 231-245

    • DOI

      10.1111/febs.16123

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In-vitro acetylation of SARS-CoV and SARS-CoV-2 nucleocapsid proteins by human PCAF and GCN52021

    • Author(s)
      Hatakeyama Dai、Masuda Takeshi、Miki Ryosuke、Ohtsuki Sumio、Kuzuhara Takashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 557 Pages: 273-279

    • DOI

      10.1016/j.bbrc.2021.03.173

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Organic synthesis and anti-influenza A virus activity of cyclobakuchiols A, B, C, and D2021

    • Author(s)
      Shoji Masaki、Esumi Tomoyuki、Tanaka Narue、Takeuchi Misa、Yamaji Saki、Watanabe Mihiro、Takahashi Etsuhisa、Kido Hiroshi、Yamamoto Masayuki、Kuzuhara Takashi
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 3 Pages: e0248960-e0248960

    • DOI

      10.1371/journal.pone.0248960

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel aqueous extract from rice fermented with Aspergillus oryzae and Saccharomyces cerevisiae possesses an anti-influenza A virus activity2021

    • Author(s)
      Shoji Masaki、Sugimoto Minami、Matsuno Kosuke、Fujita Yoko、Mii Tomohiro、Ayaki Satomi、Takeuchi Misa、Yamaji Saki、Tanaka Narue、Takahashi Etsuhisa、Noda Takeshi、Kido Hiroshi、Tokuyama Takaaki、Tokuyama Takahito、Tokuyama Takashi、Kuzuhara Takashi
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 1 Pages: e0244885-e0244885

    • DOI

      10.1371/journal.pone.0244885

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] インフルエンザウイルスRNAポリメラーゼが有するエンドヌクレアーゼ活性を阻害する化合物群2020

    • Author(s)
      畠山大、庄司正樹、葛原隆
    • Journal Title

      BIO Clinica

      Volume: 35 Pages: 73-77

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] 生命科学の最前線 精子や卵子はもういらない?ー幹細胞からの個体の構築へー2020

    • Author(s)
      葛原隆
    • Journal Title

      都薬雑誌

      Volume: 42 Pages: 20-24

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Jiadifenolide induces the expression of cellular communication network factor (CCN) genes, and CCN2 exhibits neurotrophic activity in neuronal precursor cells derived from human induced pluripotent stem cells2019

    • Author(s)
      Shoji Masaki, Ueda Masako, Nishioka Megumi, Minato Hiroki, Seki Masahide, Harada Kenichiubo Miwa, Fukuyama Yoshiyasu, Suzuki Yutaka, Aoyama Eriko, Takigawa Masaharu, Kuzuhara Takashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 519 Issue: 2 Pages: 309-315

    • DOI

      10.1016/j.bbrc.2019.09.003

    • NAID

      120006842045

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influenza A virus nucleoprotein is acetylated by histone acetyltransferases, PCAF and GCN52018

    • Author(s)
      Hatakeyama D、Shoji M、Yamayoshi S、Yoh R、Ohmi N、Takenaka S、Saitoh A、Arakaki Y、Masuda A、Komatsu T、Nagano R、Nakano M、Noda T、Kawaoka Y、Kuzuhara T
    • Journal Title

      Journal of Biological Chemistry

      Volume: in press Issue: 19 Pages: 7126-7138

    • DOI

      10.1074/jbc.ra117.001683

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Different murine-derived feeder cells alter the definitive endoderm differentiation of human induced pluripotent stem cells.2018

    • Author(s)
      Shoji M, Minato H, Ogaki S, Seki M , Suzuki Y, Kume S, Kuzuhara T.
    • Journal Title

      PLoS ONE

      Volume: 13 Issue: 7 Pages: e0201239-e0201239

    • DOI

      10.1371/journal.pone.0201239

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acetylation of lysine residues in the recombinant nucleoprotein and VP40 matrix protein of Zaire Ebolavirus by eukaryotic histone acetyltransferases.2018

    • Author(s)
      Hatakeyama D, Ohmi N, Saitoh A, Makiyama K, Morioka M, Okazaki H, Kuzuhara T
    • Journal Title

      Biochemical and Biophysical Research Communications.

      Volume: 504 Issue: 4 Pages: 635-640

    • DOI

      10.1016/j.bbrc.2018.09.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MAO-A Inhibitory Potential of Terpene Constituents from Ginger Rhizomes―A Bioactivity Guided Fractionation.2018

    • Author(s)
      Kukula-Koch W, Koch W, Czernicka L, Glowniak K, Asakawa Y, Umeyama A, Marzec Z, Kuzuhara T.
    • Journal Title

      Molecules

      Volume: 23 Issue: 6 Pages: 1301-1301

    • DOI

      10.3390/molecules23061301

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒトiPS細胞由来神経前駆細胞の神経分化におけるCCN経路の発見2021

    • Author(s)
      葛原隆、庄司正樹、関真秀、上田雅子、西岡恵、港洋希、青山絵理子、原田研一、久保美和、福山愛保、鈴木穣、滝川正春
    • Organizer
      第12回 日本CCNファミリー研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞由来神経前駆細胞の神経分化におけるCCN経路の解析2020

    • Author(s)
      葛原隆、庄司正樹、関真秀、上田雅子、西岡恵、港洋希、青山絵理子、原田研一、久保美和、福山愛保、鈴木穣、滝川正春
    • Organizer
      日本薬学会第140年会
    • Related Report
      2020 Research-status Report
  • [Presentation] アセチル化修飾によるインフルエンザウイルスRNA合成酵素の活性調節2020

    • Author(s)
      槇山今日子、畠山大、小松嗣典、齋藤彩香、廣瀬芽生、大西杏奈、緒方星陵、加賀衣恵、大槻純男、葛原隆
    • Organizer
      日本薬学会第140年会
    • Related Report
      2020 Research-status Report
  • [Presentation] バクチオールの抗インフルエンザ活性における標的宿主タンパク質の同定2020

    • Author(s)
      田中成枝、庄司正樹、増田豪、渡辺珠汎、江角朋之、大槻純男、葛原隆
    • Organizer
      日本薬学会第140年会
    • Related Report
      2020 Research-status Report
  • [Presentation] シクロバクチオールは抗インフルエンザ活性を有する2020

    • Author(s)
      田中成枝、庄司正樹、江角朋之、山本雅之、葛原隆
    • Organizer
      第59回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] バクチオールの抗インフルエンザ活性は、宿主タンパク質との結合が必要である。2020

    • Author(s)
      庄司正樹、田中成枝、増田豪、渡辺珠汎、江角朋之、大槻純男、葛原隆
    • Organizer
      第59回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒトiPS由来神経前駆細胞の神経分化におけるCCN経路の役割2020

    • Author(s)
      葛原隆、庄司正樹、関真秀、上田雅子、西岡恵、港洋希、青山絵理子、原田研一、久保美和、福山愛保、鈴木穣、滝川正春
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Short fragment RNA of XIST expressed higher in the primed state of human iPS cells.2019

    • Author(s)
      Takashi Kuzuhara, Masaki Shoji, Hiroki Minato, Soichiro Ogaki, Masahide Seki, Yutaka Suzuki, Shoen Kume
    • Organizer
      Cell Symposia: Regulatory RNAs
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ウイルスとiPS細胞のエピジェネティクスの研究2019

    • Author(s)
      葛原隆
    • Organizer
      第11回 天然物薬用研究会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] サルーシン結合タンパク質の検索2019

    • Author(s)
      葛原隆
    • Organizer
      藻類成長因子を用いた海藻栽培技術 イノベーション 第三回研究発表会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] インフルエンザウイルスPAサブユニットにおけるアセチル化標的アミノ酸残基の変異によるエンドヌクレアーゼ活性変化2019

    • Author(s)
      畠山 大,庄司正樹,小松嗣典,齋藤綾香,槇山今日子,廣瀬芽生,大西杏奈,緒方星陵,中野雅博,加賀衣恵,野田岳志,大槻純男,河岡義裕,葛原 隆
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Feeder cells affect the definitive endoderm differentiation of human iPS cells.2018

    • Author(s)
      Masaki Shoji, Hiroki Minato, Soichiro Ogaki, Masahide Seki, Yutaka Suzuki, Shoen Kume, Takashi Kuzuhara (presenter).
    • Organizer
      Stem Cell Dynamics Throughout Life: From Development to the Adult.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] インフルエンザウイルスのPAサブユニットのアセチル化修飾に伴うエンドヌクレアーゼ活性調節2018

    • Author(s)
      畠山 大,小松嗣典,齋藤綾香,大西杏奈,槇山今日子,葛原 隆
    • Organizer
      第32回インフルエンザ研究者交流の会シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] インフルエンザウイルスのPAサブユニットのアセチル化修飾によるエンドヌクレアーゼ活性調節効果2018

    • Author(s)
      畠山 大,小松嗣典,齋藤綾香,大西杏奈,槇山今日子,緒方星陵,大槻純男,葛原 隆
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] インフルエンザウイルスRNA合成酵素へのアセチル化修飾による酵素活性調節効果2018

    • Author(s)
      畠山 大,小松嗣典,齋藤綾香,大西杏奈,槇山今日子,緒方星陵,大槻純男,葛原 隆
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 異なるマウスフィーダー細胞上で培養されたヒトiPS細胞の胚体内胚葉細胞への分化効率と遺伝子発現の変化2018

    • Author(s)
      庄司正樹、港洋希、大垣総一郎、関真秀、鈴木穣、粂昭苑、葛原隆
    • Organizer
      第17回日本再生医療学会
    • Related Report
      2018 Research-status Report
  • [Remarks]

    • URL

      http://p.bunri-u.ac.jp/lab08/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks]

    • URL

      http://p.bunri-u.ac.jp/lab08/publication.html

    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗インフルエンザウイルス剤2021

    • Inventor(s)
      徳山孝、徳山孝仁、葛原隆、庄司正樹
    • Industrial Property Rights Holder
      徳山孝、徳山孝仁
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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