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Critical epigenome identification of human iPS / ES cells based on machine learning analysis of teratoma pathology

Research Project

Project/Area Number 15H04715
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Umezawa Akihiro  国立研究開発法人国立成育医療研究センター, 再生医療センター, 副所長/再生医療センター長 (70213486)

Co-Investigator(Kenkyū-buntansha) 豊田 雅士  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究副部長 (50392486)
中井 謙太  東京大学, 医科学研究所, 教授 (60217643)
秦 順一  公益財団法人実験動物中央研究所, その他部局等, 所長 (90051614)
Project Period (FY) 2015-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords奇形腫 / システム病理学 / 多能性幹細胞 / ES細胞 / エピゲノム / メチル化解析 / ヒト幹細胞 / 人体バイオリソース / 再生医療 / 泌尿生殖器・内分泌 / 機械学習 / ディープラーニング / クリティカルエピゲノム
Outline of Final Research Achievements

Machine learning analysis was performed on the histopathological image of the teratoma. The critical epigenome of pluripotent stem cells was identified. We analyzed the process of teratoma formation, the interaction between cells, and the site of transplantation. We also clarified the process of forming a teratoma. We attempted to elucidate the structure of teratomas caused by pluripotent stem cells. System pathology is characterized by the elucidation of the mechanisms and principles of cells, organs, and multicellular bodies. It has become possible to elucidate the mechanism of cells and genes that are difficult with conventional methods

Academic Significance and Societal Importance of the Research Achievements

現代病理学・幹細胞学の研究は、物質レベルで腫瘍の構成要素を明らかにし、発生部位における組織像の差異を明らかにするという要素還元的アプローチが主流である。その結果、ゲノム情報や細胞を構成する分子とその機能に関する多くの知識が蓄積されてきた。さらに病理学をシステムとしてとらえ、構成する要素間の相互作用がもたらすダイナミクス、制御ネットワークの解明するシステムが展開された。本研究においては、構成的システム病理学的手法を用いて、多能性幹細胞を移植することで形成された奇形腫に対して、組織構成及び未分化度・悪性化を創成する仕組みや原理を解明するところに特徴があり、学術的な意義は極めて高い。

Report

(6 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (3 results)

All 2018 2016 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Remarks (1 results)

  • [Journal Article] Epigenetic-scale comparison of human iPSCs generated by retrovirus, Sendai virus or episomal vectors2018

    • Author(s)
      Nishino Koichiro、Arai Yoshikazu、Takasawa Ken、Toyoda Masashi、Yamazaki-Inoue Mayu、Sugawara Tohru、Akutsu Hidenori、Nishimura Ken、Ohtaka Manami、Nakanishi Mahito、Umezawa Akihiro
    • Journal Title

      Regenerative Therapy

      Volume: 9 Pages: 71-78

    • DOI

      10.1016/j.reth.2018.08.002

    • NAID

      120007128469

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] OpenTein: a database of digital whole-slide images of stem cell-derived teratomas.2016

    • Author(s)
      Park SJ, Komiyama Y, Suemori H, Umezawa A, Nakai K.
    • Journal Title

      Nucleic Acids Res.

      Volume: 44 Issue: D1 Pages: D1000-D1004

    • DOI

      10.1093/nar/gkv1096

    • NAID

      120006305899

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Remarks] OpenTein

    • URL

      http://opentein.hgc.jp/

    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2022-11-04  

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