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Molecular mechanism in hematopoiesis of arachnoid cell induced by pulsatile flow

Research Project

Project/Area Number 19K22679
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Youichiro Wada  東京大学, アイソトープ総合センター, 教授 (10322033)

Co-Investigator(Kenkyū-buntansha) 和田 裕美  東京大学, アイソトープ総合センター, 特任研究員 (60645042)
中戸 隆一郎  東京大学, 定量生命科学研究所, 講師 (60583044)
中田 庸一  東京大学, アイソトープ総合センター, 特任助教 (40584793)
Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsくも膜 / シェアストレス / エピゲノム / 幹細胞
Outline of Research at the Start

脳血管は外膜や栄養血管を欠き、平滑筋層外側にくも膜細胞がクモの巣のように位置して血管を取囲み支える。くも膜組織が脳血管システム維持に担う役割、病的環境下での内皮細胞への分化とTGFbeta経路の関与を報告してきた。くも膜における造血能という別の分化経路に着目するに至り、拍動流刺激による造血能関連遺伝子群の誘導を確認した。本研究は力学的刺激を中心とする分化誘導環境下でこの誘導メカニズムの解明を目指す。多能性分化能を有するヒトくも膜細胞の生理的機能に関する理解を深めることにより、培養くも膜細胞移植による脳血管障害の機能予後改善や、体外造血といった臨床応用の可能性に挑戦する。

Outline of Final Research Achievements

As a result of intravenous administration of primary cultured rat arachnoid cells to rats exposed to lethal radiation, all rats survived for more than one year, suggesting the possibility of hematopoietic potential in arachnoid tissues. Using primary cultured human arachnoid cells, pulsatile flow stimulation under a mixed culture system induced a group of genes related to hematopoietic potential. Based on these results, we established an experimental system to elucidate the molecular mechanism of differentiation in an environment where mechanical stimulation is mainly used to induce differentiation. Integrative omics analysis of transcriptome data of cultured human arachnoid cells obtained in this experimental system confirmed the induction of a series of differentiation genes reported in hematopoietic differentiation from endothelium, and the transcriptional cascade was successfully identified.

Academic Significance and Societal Importance of the Research Achievements

脳血管システムにおけるくも膜細胞の役割において、血管系細胞との相互作用及び内皮細胞への分化能を示唆する所見に加え、本研究では造血能を有する可能性が示された。
こうしたくも膜細胞の多分化能によって、脳血管システムを超えた全身の恒常性維持に関与していることが明らかになれば、頭蓋内外における造血システムの解明及び治療法開発に向けた応用を目指すことが可能となる。また、培養くも膜細胞の臨床応用は、iPS細胞等とは異なる生体の自己修復能の応用技術の開発という意味で、今後の再生医療における新たな一領域の開拓という意義があると考えている。

Report

(2 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )

Research Products

(12 results)

All 2021 2020

All Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 9 results,  Open Access: 7 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion Injury2021

    • Author(s)
      Hasegawa S, Inoue T, Nakamura Y, Fukaya D, Uni R, Wu CH, Fujii R, Peerapanyasut W, Taguchi A, Kohro T, Yamada S, Katagiri M, Ko T, Nomura S, Nakanishi Ozeki A, Susaki EA, Ueda HR, Akimitsu N, Wada Y, Komuro I, Nangaku M, Inagi R.
    • Journal Title

      Journal of the American Society of Nephrology

      Volume: -

    • DOI

      10.1681/asn.2020121723

    • NAID

      120007174517

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PERK inhibition attenuates vascular remodeling in pulmonary arterial hypertension caused by BMPR2 mutation2021

    • Author(s)
      Shimizu Takashi、Higashijima Yoshiki、Kanki Yasuharu、Nakaki Ryo、Kawamura Takeshi、Urade Yoshihiro、Wada Youichiro
    • Journal Title

      Science Signaling

      Volume: 14

    • DOI

      10.1126/scisignal.abb3616

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PERK participates in cardiac valve development via fatty acid oxidation and endocardial-mesenchymal transformation2020

    • Author(s)
      Shimizu Takashi、Maruyama Kazuaki、Kawamura Takeshi、Urade Yoshihiro、Wada Youichiro
    • Journal Title

      Sci Rep

      Volume: 10 Pages: 20094-20094

    • DOI

      10.1038/s41598-020-77199-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysine demethylase 7a regulates murine anterior-posterior development by modulating the transcription of Hox gene cluster2020

    • Author(s)
      Higashijima Yoshiki、Nagai Nao、Yamamoto Masamichi、Kitazawa Taro、Kawamura Yumiko K.、Taguchi Akashi、Nakada Natsuko、Nangaku Masaomi、Furukawa Tetsushi、Aburatani Hiroyuki、Kurihara Hiroki、Wada Youichiro、Kanki Yasuharu
    • Journal Title

      Commun Biol

      Volume: 3 Pages: 725-725

    • DOI

      10.1038/s42003-020-01456-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PERK-Mediated Suppression of microRNAs by Sildenafil Improves Mitochondrial Dysfunction in Heart Failure2020

    • Author(s)
      Shimizu Takashi、Taguchi Akashi、Higashijima Yoshiki、Takubo Naoko、Kanki Yasuharu、Urade Yoshihiro、Wada Youichiro
    • Journal Title

      iScience

      Volume: 23 Pages: 101410-101410

    • DOI

      10.1016/j.isci.2020.101410

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vagus nerve stimulation even after injury ameliorates cisplatin-induced nephropathy via reducing macrophage infiltration2020

    • Author(s)
      Uni Rie、Inoue Tsuyoshi、Nakamura Yasuna、Fukaya Daichi、Hasegawa Sho、Wu Chia-Hsien、Fujii Rie、Surattichaiyakul Bongkod、Peerapanyasut Wachirasek、Ozeki Atsuko、Akimitsu Nobuyoshi、Wada Youichiro、Nangaku Masaomi、Inagi Reiko
    • Journal Title

      Scientific Reports

      Volume: 10 Pages: 9472-9472

    • DOI

      10.1038/s41598-020-66295-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stability of RNA sequences derived from the coronavirus genome in human cells2020

    • Author(s)
      Wakida Hiroyasu、Kawata Kentaro、Yamaji Yuta、Hattori Emi、Tsuchiya Takaho、Wada Youichiro、Ozaki Haruka、Akimitsu Nobuyoshi
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 527 Pages: 993-999

    • DOI

      10.1016/j.bbrc.2020.05.008

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells2020

    • Author(s)
      Higashijima Y, Matsui Y, Shimamura T, Nakaki R, Nagai N, Tsutsumi S, Abe Y, Link VM, Osaka M, Yoshida M, Watanabe R, Tanaka T, Taguchi A, Miura M, Ruan X, Li G, Inoue T, Nangaku M, Kimura H, Furukawa T, Aburatani H, Wada Y, Ruan Y, Glass CK, Kanki Y
    • Journal Title

      EMBO Journal

      Volume: 39 Pages: 1-1

    • DOI

      10.15252/embj.2019103949

    • NAID

      120006902140

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Toward understanding the dynamic state of 3D genome2020

    • Author(s)
      Shinkai S, Onami S, Nakato R.
    • Journal Title

      Computational and Structural Biotechnology Journal

      Volume: 18 Pages: 2259-2269

    • DOI

      10.1016/j.csbj.2020.08.014

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 群雄割拠のシングルセル情報解析:現状把握とその先2020

    • Author(s)
      中戸 隆一郎
    • Organizer
      第9回生命医薬情報学連合大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Large-scale analysis of multi-omics data toward the elucidation of epigenomic diversity2020

    • Author(s)
      中戸 隆一郎
    • Organizer
      第2回 ASHBi数理生物研究集会
    • Related Report
      2020 Annual Research Report
  • [Book] クロマチン解析実践プロトコール2020

    • Author(s)
      大川 恭行、宮成 悠介
    • Total Pages
      270
    • Publisher
      羊土社
    • ISBN
      9784758122481
    • Related Report
      2020 Annual Research Report

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Published: 2019-07-04   Modified: 2022-01-27  

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