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Plasma cell-free DNA and RNA analysis of astronauts for evaluation of space environmental responses

Research Project

Project/Area Number 20H03234
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43050:Genome biology-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Muratani Masafumi  筑波大学, 医学医療系, 教授 (50730199)

Co-Investigator(Kenkyū-buntansha) 高橋 智  筑波大学, 医学医療系, 教授 (50271896)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2022: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Keywords宇宙環境 / リキッドバイオプシー / オミックス解析 / セルフリーDNA・RNA / エピゲノム解析 / RNAシークエンシング
Outline of Research at the Start

血液中には体内の細胞から放出された核酸(DNA、RNA)が循環しており、比較的容易に検体が採取できることから、疾患や生体応答のモニタリング法として利用できる。本研究では、この手法を宇宙飛行士の参加する臨床研究に応用し、宇宙環境における体内組織の変化を調査する。同様の手法はこれまでにマウスを用いた宇宙フライト実験でも行われており、その過程で得られた知見をヒトでも確認できると期待される。宇宙滞在中に起きる筋萎縮や骨量の減少など、ヒトの老化と共通した現象の分子メカニズムの解明につながる可能性がある。

Outline of Final Research Achievements

Blood samples were collected from 6 astronauts at 11 time points to compare pre-flight baseline, in-flight and post-flight conditions. Consistent with the report from the Twins Study, we observed a significant increase in cell-free mitochondrial DNA in plasma during space flight. Mitochondria-enriched fractions were isolated by surface markers of extracellular vesicles, and RNA-sequencing was performed. The results showed enrichment of tissue-specific RNAs derived from various tissues including cardiovascular and nervous systems, indicating that these tissues are under metabolic stress in space. These results also established successful monitoring of internal tissues using cfRNA-based liquid biopsies.

Academic Significance and Societal Importance of the Research Achievements

宇宙の微小重力環境は、地球生命がこれまで経験したことの無い環境に対してどのように応答するのかを観察できるユニークな条件であり、その応答としてミトコンドリア応答が体内でシステミックに起こることがマウスとヒトの両方で示された。これらの応答はヒトの地上での代謝関連疾患等とも関連していると考えられ、宇宙で顕在化する制御機構が地上での医学や基礎生命科学の進歩に寄与することが期待される。また、本研究で得られた知見はヒトの長期宇宙滞在や月、火星への有人ミッションに向けた宇宙医学研究に寄与する。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (24 results)

All 2022 2021 2020 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Open Access: 7 results,  Peer Reviewed: 6 results) Presentation (6 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Remarks (5 results)

  • [Int'l Joint Research] NASA Ames Research Center/Weill Cornell Medicine/Ohio University(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University College London(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] KTH Royal Institute of Technology(スウェーデン)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Routine omics collection is a golden opportunity for European human research in space and analog environments2022

    • Author(s)
      Cope Henry、Willis Craig R.G.、MacKay Matthew J.、Rutter Lindsay A.、Toh Li Shean、Williams Philip M.、Herranz Ra?l、Borg Joseph、Bezdan Daniela、Giacomello Stefania、Muratani Masafumi、Mason Christopher E.、Etheridge Timothy、Szewczyk Nathaniel J.
    • Journal Title

      Patterns

      Volume: 3 Issue: 10 Pages: 100550-100550

    • DOI

      10.1016/j.patter.2022.100550

    • Related Report
      2022 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Transcriptome analysis of gravitational effects on mouse skeletal muscles under microgravity and artificial 1 g onboard environment2021

    • Author(s)
      Risa Okada, 他15名, Naoki Ito, Dai Shiba, Masaki Shirakawa, Masafumi Muratani, Takashi Kudo, Satoru Takahashi.
    • Journal Title

      Scientific reports

      Volume: 11 Issue: 1 Pages: 9168-9168

    • DOI

      10.1038/s41598-021-88392-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nuclear factor E2-related factor 2 (NRF2) deficiency accelerates fast fibre type transition in soleus muscle during space flight2021

    • Author(s)
      Hayashi Takuto, Kudo Takashi, Fujita Ryo, Fujita Shin-ichiro, Tsubouchi Hirona, Fuseya Sayaka, Suzuki Riku, Hamada Michito, Okada Risa, Muratani Masafumi, Shiba Dai, Suzuki Takafumi, Warabi Eiji, Yamamoto Masayuki, Takahashi Satoru
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 787-787

    • DOI

      10.1038/s42003-021-02334-4

    • NAID

      120007185357

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intergenerational effect of short-term spaceflight in mice2021

    • Author(s)
      Yoshida Keisuke、Fujita Shin-ichiro、Isotani Ayako、Kudo Takashi、Takahashi Satoru、Ikawa Masahito、Shiba Dai、Shirakawa Masaki、Muratani Masafumi、Ishii Shunsuke
    • Journal Title

      iScience

      Volume: 24 Issue: 7 Pages: 102773-102773

    • DOI

      10.1016/j.isci.2021.102773

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 宇宙生命科学研究におけるオミックス解析の標準化・自動化と国際連携2021

    • Author(s)
      Lindsay Rutter, 村谷匡史
    • Journal Title

      医学のあゆみ

      Volume: 279 Pages: 623-623

    • Related Report
      2021 Annual Research Report
  • [Journal Article] リキッドバイオプシー解析を介したモデル生物研究成果のヒトへの投射2021

    • Author(s)
      村谷匡史
    • Journal Title

      医学のあゆみ

      Volume: 279 Pages: 647-647

    • Related Report
      2021 Annual Research Report
  • [Journal Article] MicroRNA-196a-5p in Extracellular Vesicles Secreted from Myoblasts Suppresses Osteoclast-like Cell Formation in Mouse Cells2020

    • Author(s)
      Takafuji Yoshimasa、Tatsumi Kohei、Kawao Naoyuki、Okada Kiyotaka、Muratani Masafumi、Kaji Hiroshi
    • Journal Title

      Calcified Tissue International

      Volume: 108 Pages: 364-376

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrated RNA-seq Analysis Indicates Asynchrony in Clock Genes between Tissues under Spaceflight2020

    • Author(s)
      Fujita Shin-ichiro、Rutter Lindsay、Ong Quang、Muratani Masafumi
    • Journal Title

      Life

      Volume: 10 Pages: 196-196

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A New Era for Space Life Science: International Standards for Space Omics Processing2020

    • Author(s)
      Rutter Lindsay、Barker Richard、Bezdan Daniela、他13名、Galazka Jonathan M.、Herranz Raul、Muratani Masafumi
    • Journal Title

      Patterns

      Volume: 1 Pages: 100148-100148

    • Related Report
      2020 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration2020

    • Author(s)
      Afshinnekoo Ebrahim、Scott Ryan T.、MacKay Matthew J.、Pariset Eloise、Cekanaviciute Egle、Barker Richard、Gilroy Simon、Hassane Duane、Smith Scott M.、Zwart Sara R.、Nelman-Gonzalez Mayra、Crucian Brian E.、Ponomarev Sergey A.、Orlov Oleg I.、Shiba Dai、Muratani Masafumi、Yamamoto Masayuki、以降著者省略
    • Journal Title

      Cell

      Volume: 183 Issue: 5 Pages: 1162-1184

    • DOI

      10.1016/j.cell.2020.10.050

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Space life science research to predict the future of life on and beyond Earth2022

    • Author(s)
      Muratani M
    • Organizer
      GeneLab Analysis Working Group Symposium 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tissue deconvolution and cross-species analysis of plasma cell-free RNA highlight homeostatic throwback phenotypes in space2022

    • Author(s)
      Rutter L, Husna N, Aiba T, Fujita SI, Saito Y, Shiba D, Kudo T, Takahashi S, Furukawa S, Muratani M
    • Organizer
      ISS R&D Conference 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular characterization of space environment responses in internal tissues by cell-free DNA and RNA analysis of plasma samples collected from six astronauts2022

    • Author(s)
      Rutter L. Husna N, Fujita SI, Saito Y, Kudo T, Takahashi S, Muratani M
    • Organizer
      American Society for Gravity and Space Research (ASGSR) Annual Conference 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification and validation of multi-omics frailty biomarkers in human spaceflight2022

    • Author(s)
      Camera A, Galsinh AS, Kim JK, Barker RJ, Enguita FJ, Tabetah M, Seylani A, Laiakis EC, Finch RH, Das S, Arif S, Zaksas V, Goel C, Senarath CS, Kim MS, Karouia F, Szewczyk NJ, Porterfield M, Muratani M, Mason CE, Beheshti A
    • Organizer
      American Society for Gravity and Space Research (ASGSR) Annual Conference 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 宇宙研究からアプローチする適応・進化の理解と地球生命の未来予測2022

    • Author(s)
      村谷匡史
    • Organizer
      第45回日本分子生物学会年会,ワークショップ,クロマチン潜在能に働きかけるエピゲノムと核内構造体
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 宇宙飛行士のリキッドバイオプシー解析から見た宇宙環境応答の多臓器連環2021

    • Author(s)
      村谷匡史, Lindsay Rutter, 藤田晋一郎, 高橋智
    • Organizer
      日本宇宙生物科学会第35回大会
    • Related Report
      2021 Annual Research Report
  • [Remarks] GeneLab, OSD-530, Cell-free RNA analysis

    • URL

      https://osdr.nasa.gov/bio/repo/data/studies/OSD-530

    • Related Report
      2022 Annual Research Report
  • [Remarks] GeneLab, OSD-532, Space flight mouse plasma cfRNA

    • URL

      https://osdr.nasa.gov/bio/repo/data/studies/OSD-532

    • Related Report
      2022 Annual Research Report
  • [Remarks] 宇宙生命科学研究の国際コンソーシアム設立~筑波大学開発の解析技術を世界で活用~

    • URL

      https://www.tsukuba.ac.jp/journal/medicine-health/20201126124330.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] きぼう利用シンポジウム2021

    • URL

      https://iss-kibo.space/2020/profile.html#2-2-2

    • Related Report
      2020 Annual Research Report
  • [Remarks] 宇宙滞在中の液体生検による血漿中核酸のゲノム・エピゲノム解析

    • URL

      https://humans-in-space.jaxa.jp/kibouser/subject/life/70721.html

    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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