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Sex differences during differentiation of pluripotent stem cells

Research Project

Project/Area Number 20K06454
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42030:Animal life science-related
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

Mawaribuchi Shuuji  国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (70554921)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords多能性幹細胞 / 長期継代 / 上皮間葉転換 / 性差
Outline of Research at the Start

再生医療では迅速かつ安全な治療のため、品質の高い様々な種類の多能性幹細胞(iPS/ES細胞)をバンク化し、他家移植することが進められている。その際、治療目的に沿う細胞の性質(分化効率の良さなど)を持つ細胞の選定が必要であり、申請者は多能性幹細胞の性質(品質)に影響を与える要素として男女差に注目した。多能性幹細胞で上皮間葉転換や三胚葉分化の効率に男女差が生じるメカニズムなどを解析することで、細胞バンクで治療目的に沿った性質の細胞を選定することに利用可能な分子マーカーを探索する。

Outline of Final Research Achievements

The sex difference influences the properties of pluripotent stem cells. X chromosome is inactivated in female pluripotent stem cells, but long-term passaging results in incomplete inactivation of the X chromosome. The incomplete inactivation induces sex differences in gene expression on the X chromosome, and female-derived pluripotent stem cells are resistant to differentiation. RNAseq analysis of long-term passage of female-derived pluripotent stem cells revealed that the expression level of a gene increased with passage. This gene is known to be involved in the inhibition of neuronal differentiation and may be a molecular marker for differentiation resistance.

Academic Significance and Societal Importance of the Research Achievements

再生医療等製品では迅速かつ安全な治療のため、品質の高い様々な種類の多能性幹細胞(iPS/ES細胞)をバンク化し、他家移植することが進められている。その際、治療目的に沿う細胞の性質(分化効率の良さなど)を持つ細胞の選定が必要である。X染色体の不活性化が不完全になった女性由来多能性幹細胞は分化抵抗性を示す。この分化抵抗性を示す分子マーカーを探索することは、再生医療等製品の各製造プロセスにおける品質管理技術において重要である。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (19 results)

All 2024 2023 2022 2021 2020

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 6 results) Presentation (8 results)

  • [Journal Article] Multiple Transitions between Y Chromosome and Autosome in Tago’s Brown Frog Species Complex2024

    • Author(s)
      Miura Ikuo、Shams Foyez、Ohki Jun’ichi、Tagami Masataka、Fujita Hiroyuki、Kuwana Chiao、Nanba Chiyo、Matsuo Takanori、Ogata Mitsuaki、Mawaribuchi Shuuji、Shimizu Norio、Ezaz Tariq
    • Journal Title

      Genes

      Volume: 15 Issue: 3 Pages: 300-300

    • DOI

      10.3390/genes15030300

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Parallel Evolution of Sex-Linked Genes across XX/XY and ZZ/ZW Sex Chromosome Systems in the Frog Glandirana rugosa2023

    • Author(s)
      Mawaribuchi Shuuji、Ito Michihiko、Ogata Mitsuaki、Yoshimura Yuri、Miura Ikuo
    • Journal Title

      Genes

      Volume: 14 Issue: 2 Pages: 257-257

    • DOI

      10.3390/genes14020257

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] rBC2LCN-reactive SERPINA3 is a glycobiomarker candidate for pancreatic ductal adenocarcinoma2023

    • Author(s)
      Mawaribuchi Shuuji、Shimomura Osamu、Oda Tatsuya、Hiemori Keiko、Shimizu Kayoko、Yamase Kenya、Date Mutsuhiro、Tateno Hiroaki
    • Journal Title

      Glycobiology

      Volume: cwad009 Issue: 4 Pages: 342-352

    • DOI

      10.1093/glycob/cwad009

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evolutionary features of ligands and their receptors via protein-protein interactions and essentiality in primates2023

    • Author(s)
      Mawaribuchi Shuuji、Haramoto Yoshikazu、Ikeda Nozomi、Ito Michihiko
    • Journal Title

      Genes to Cells

      Volume: 28 Issue: 4 Pages: 258-266

    • DOI

      10.1111/gtc.13006

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of ancestral sex chromosomes in the frog Glandirana rugosa bearing XX‐XY and ZZ‐ZW sex‐determining systems2022

    • Author(s)
      Miura Ikuo、Shams Foyez、Jeffries Daniel Lee、Katsura Yukako、Mawaribuchi Shuuji、Perrin Nicolas、Ito Michihiko、Ogata Mitsuaki、Ezaz Tariq
    • Journal Title

      Molecular Ecology

      Volume: 31 Issue: 14 Pages: 3859-3870

    • DOI

      10.1111/mec.16551

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Highly rapid and diverse sex chromosome evolution in the Odorrana frog species complex2022

    • Author(s)
      Katsumi Taito、Shams Foyez、Yanagi Hiroaki、Ohnishi Taku、Toda Mamoru、Lin Si‐Min、Mawaribuchi Shuuji、Shimizu Norio、Ezaz Tariq、Miura Ikuo
    • Journal Title

      Development, Growth & Differentiation

      Volume: 64 Issue: 6 Pages: 279-289

    • DOI

      10.1111/dgd.12800

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fibroblastic reticular cells and type 3 innate lymphoid cells in Peyer’s patches: Target cell candidates for inulooligosaccharides in hochuekkito formula containing Atractylodis rhizoma2022

    • Author(s)
      Takuya Maeda, Haruna Hosaka, Yuki Nakamura, Shuuji Mawaribuchi, Takayuki Nagai, Mari Endo, Naoki Ito, Hiroaki Kiyohara
    • Journal Title

      Traditional & Kampo Medicine

      Volume: 9 Issue: 1 Pages: 32-40

    • DOI

      10.1002/tkm2.1307

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Independent pseudogenizations and losses of sox15 during amniote diversification following asymmetric ohnolog evolution2021

    • Author(s)
      Yusaku Ogita, Kei Tamura, Shuuji Mawaribuchi, Nobuhiko Takamatsu, Michihiko Ito
    • Journal Title

      BMC ecology and evolution

      Volume: 21 Issue: 1 Pages: 134-134

    • DOI

      10.1186/s12862-021-01864-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] rBC2LCN lectin as a potential probe of early‐stage HER2‐positive breast carcinoma2020

    • Author(s)
      Mawaribuchi Shuuji、Haramoto Yoshikazu、Tateno Hiroaki、Onuma Yasuko、Aiki Yasuhiko、Ito Yuzuru
    • Journal Title

      FEBS Open Bio

      Volume: 10 Issue: 6 Pages: 1056-1064

    • DOI

      10.1002/2211-5463.12852

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A technique for removing tumourigenic pluripotent stem cells using rBC2LCN lectin2020

    • Author(s)
      Haramoto Yoshikazu、Onuma Yasuko、Mawaribuchi Shuuji、Nakajima Yoshiro、Aiki Yasuhiko、Higuchi Kumiko、Shimizu Madoka、Tateno Hiroaki、Hirabayashi Jun、Ito Yuzuru
    • Journal Title

      Regenerative Therapy

      Volume: 14 Pages: 306-314

    • DOI

      10.1016/j.reth.2020.03.017

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SSEA-1-positive fibronectin is secreted by cells deviated from the undifferentiated state of human induced pluripotent stem cells2020

    • Author(s)
      Watanabe Tomoko、Saito Sayoko、Hiemori Keiko、Kiyoi Kayo、Mawaribuchi Shuuji、Haramoto Yoshikazu、Tateno Hiroaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 529 Issue: 3 Pages: 575-581

    • DOI

      10.1016/j.bbrc.2020.06.074

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 膵疾患の新規バイオマーカーの最新の話題 早期膵癌を検出する新規バイオマーカー候補rBC2LCN-SerpinA3"BC2-S3"2023

    • Author(s)
      下村 治, 回渕 修治, 舘野 浩章, 比江森 恵子, 山瀬 堅也, 木戸脇 佳代子, 宮崎 貴寛, 土井 愛美, 橋本 真治, 小田 竜也
    • Organizer
      第54回日本膵臓学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 哺乳類の性決定遺伝子Sryの分子進化:真獣哺乳類祖先~現存種2023

    • Author(s)
      奥山ほのか, 稲積しおり, 荻田悠作, 井口竣友, 回渕修治, 林舜, 須田皓介, 田村啓, 塚本大輔, 松尾拓哉, 伊藤道彦
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 乳がん培養細胞と間葉系幹細胞の細胞融合によるがんの悪性化の解析2023

    • Author(s)
      回渕修治, 原本悦和
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] iPS細胞から生じた低品質細胞の非破壊検出および除去技術の開発2023

    • Author(s)
      渡邊 朋子, 回渕 修治, 原本 悦和, 舘野 浩章
    • Organizer
      長岡バイオ エコノミーシンポジウム2024
    • Related Report
      2023 Annual Research Report
  • [Presentation] タゴガエル種群の性染色体進化:Y染色体の種間移動とその起源2023

    • Author(s)
      三浦郁夫, Foyez Shams, 大木淳一, 青西靖夫, 林浩介, 田上正隆, 藤田宏之, 桑名知碧, 回渕 修治, Tariq Ezaz
    • Organizer
      日本爬虫両棲類学会第62回船橋大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] iPS細胞から生じた低品質細胞の非破壊検出および除去技術の開発2023

    • Author(s)
      渡邊 朋子, 回渕 修治, 原本 悦和, 舘野 浩章
    • Organizer
      日本再生医療学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 多能性幹細胞の個性(分化指向性と男女差)と品質管理2021

    • Author(s)
      回渕修治
    • Organizer
      第19回 産総研・産技連LS-BT合同研究発表会
    • Related Report
      2021 Research-status Report
  • [Presentation] ヒト人工多能性幹細胞の品質管理技術の開発2021

    • Author(s)
      渡邊 朋子、角太 淳吾、回渕 修治、原本 悦和、今井 俊夫、舘野 浩章
    • Organizer
      第19回 産総研・産技連LS-BT合同研究発表会
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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