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Information coding based in cell-to-cell variability

Research Project

Project/Area Number 21H04759
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Kuroda Shinya  東京大学, 大学院理学系研究科(理学部), 教授 (50273850)

Project Period (FY) 2021-04-05 – 2024-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥43,030,000 (Direct Cost: ¥33,100,000、Indirect Cost: ¥9,930,000)
Fiscal Year 2023: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2022: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
Fiscal Year 2021: ¥22,620,000 (Direct Cost: ¥17,400,000、Indirect Cost: ¥5,220,000)
Keywordsトランスオミクス / 肝臓ゾネーション / ゾネーション / 1細胞 / 情報量 / 1細胞 / 細胞不均一性
Outline of Research at the Start

本研究では、これまで別々に解析されてきた、I.1細胞レベルの情報コードと、II.空間的細胞間不均一性(ゾネーション)を組み合わせることにより、組織がゾネーションをどのように利用して情報を正確かつロバストに伝達しているのか、逆に空間情報的に細胞間の不均一性を最適に配置された結果がゾネーションであるかを明らかにする。

Outline of Final Research Achievements

We performed trans-omics analysis of liver zonation to decode spatial information from cellular heterogeneity. We reanalyzed previously reported transcriptomic and proteomic data, initially divided into eight zones within hepatic lobules, using a trans-omics approach. Our analysis indicated that reclassification into four areas (peri-central, mid-central, mid-portal, peri-portal) was more appropriate. This led to the discovery of novel functional characteristics specific to the central region of the hepatic lobule. Furthermore, we identified distinct spatial patterns in metabolism: carbohydrate and amino acid metabolism monotonically increased toward the peri-portal region, whereas lipid metabolism monotonically increased toward the peri-central region.

Academic Significance and Societal Importance of the Research Achievements

本研究は肝臓ゾネーション解析を従来より高精度な4エリア区分で実施し、単調的な遺伝子発現パターンを明確化したことで、肝臓代謝機能の空間的特性の理解を飛躍的に深めた。また、ゾネーション異常に関連する肝疾患の病態解明や治療戦略開発に寄与する可能性を示し、医学・薬学分野への重要な基盤を提供した。

Report

(5 results)
  • 2024 Final Research Report ( PDF )
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • 2021 Comments on the Screening Results   Annual Research Report
  • Research Products

    (28 results)

All 2025 2024 2023 2022 2021

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 11 results) Presentation (16 results) (of which Int'l Joint Research: 8 results,  Invited: 12 results) Book (1 results)

  • [Journal Article] Model selection reveals selective regulation of blood amino acid and lipid metabolism by insulin in humans.2024

    • Author(s)
      Fujita, S., Hironaka, K., Karasawa, Y., Kuroda, S.
    • Journal Title

      iScience

      Volume: 27(6) Issue: 6 Pages: 109833-109833

    • DOI

      10.1016/j.isci.2024.109833

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Time and dose selective glucose metabolism for glucose homeostasis and energy conversion in the liver2024

    • Author(s)
      Pan Yifei、Hatano Atsushi、Ohno Satoshi、Morita Keigo、Kokaji Toshiya、Bai Yunfan、Sugimoto Hikaru、Egami Riku、Terakawa Akira、Li Dongzi、Uematsu Saori、Maehara Hideki、Fujita Suguru、Inoue Hiroshi、Inaba Yuka、Nagano Atsushi J.、Hirayama Akiyoshi、Soga Tomoyoshi、Kuroda Shinya
    • Journal Title

      npj Systems Biology and Applications

      Volume: 10 Issue: 1 Pages: 107-107

    • DOI

      10.1038/s41540-024-00437-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] iTraNet: a web-based platform for integrated trans-omics network visualization and analysis2024

    • Author(s)
      Sugimoto Hikaru、Morita Keigo、Li Dongzi、Bai Yunfan、Mattanovich Matthias、Kuroda Shinya
    • Journal Title

      Bioinformatics Advances

      Volume: 4 Issue: 1

    • DOI

      10.1093/bioadv/vbae141

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity.2024

    • Author(s)
      Bai Y, Morita K, Kokaji T, Hatano A, Ohno S, Egami R, Pan Y, Li D, Yugi K, Uematsu S, Inoue H, Inaba Y, Suzuki Y, Matsumoto M, Takahashi M, Izumi Y, Bamba T, Hirayama A, Soga T, Kuroda S*.
    • Journal Title

      iScience

      Volume: 27(3) Issue: 3 Pages: 109121-109121

    • DOI

      10.1016/j.isci.2024.109121

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle2023

    • Author(s)
      Maehara H.、Kokaji T.、Hatano A.、Suzuki Y.、Matsumoto M.、Nakayama K. I.、Egami R.、Tsuchiya T.、Ozaki H.、Morita K.、Shirai M.、Li D.、Terakawa A.、Uematsu S.、Hironaka K.、Ohno S.、Kubota H.、Araki H.、Miura F.、Ito T.、Kuroda S.
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 19118-19118

    • DOI

      10.1038/s41598-023-46393-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DI/cle , a Measure Consisting of Insulin Sensitivity, Secretion, and Clearance, Catures Diabetic States2023

    • Author(s)
      3.Sugimoto, H., Hironaka, K., Yamada, T., Sakaguchi, K., Ogawa, W., and Kuroda, S.
    • Journal Title

      The Journal of Clinical Endocrinology & Metabolism

      Volume: 108(12) Issue: 12 Pages: 3080-3089

    • DOI

      10.1210/clinem/dgad392

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optogenetic decoding of Akt2-regulated metabolic signaling pathways in skeletal muscle cells using transomics analysis2023

    • Author(s)
      Kawamura Genki、Kokaji Toshiya、Kawata Kentaro、Sekine Yuka、Suzuki Yutaka、Soga Tomoyoshi、Ueda Yoshibumi、Endo Mizuki、Kuroda Shinya、Ozawa Takeaki
    • Journal Title

      Science Signaling

      Volume: 16 Issue: 773 Pages: 773-773

    • DOI

      10.1126/scisignal.abn0782

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Features extracted using tensor decomposition reflect the biological features of the temporal patterns of human blood multimodal metabolome2023

    • Author(s)
      Fujita Suguru、Karasawa Yasuaki、Hironaka Ken-ichi、Taguchi Y.-h.、Kuroda Shinya
    • Journal Title

      PLOS ONE

      Volume: 18 Issue: 2 Pages: e0281594-e0281594

    • DOI

      10.1371/journal.pone.0281594

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trans-omics analysis of insulin action reveals a cell growth subnetwork which co-regulates anabolic processes2022

    • Author(s)
      Terakawa Akira、Hu Yanhui、Kokaji Toshiya、Yugi Katsuyuki、Morita Keigo、Ohno Satoshi、Pan Yifei、Bai Yunfan、Parkhitko Andrey A.、Ni Xiaochun、Asara John M.、Bulyk Martha L.、Perrimon Norbert、Kuroda Shinya
    • Journal Title

      iScience

      Volume: 25 Issue: 5 Pages: 104231-104231

    • DOI

      10.1016/j.isci.2022.104231

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantitative metabolic fluxes regulated by trans-omic networks2022

    • Author(s)
      Ohno Satoshi、Uematsu Saori、Kuroda Shinya
    • Journal Title

      Biochemical Journal

      Volume: 479 Issue: 6 Pages: 787-804

    • DOI

      10.1042/bcj20210596

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism2022

    • Author(s)
      Uematsu Saori、Ohno Satoshi、Tanaka Kaori Y.、Hatano Atsushi、Kokaji Toshiya、Ito Yuki、Kubota Hiroyuki、Hironaka Ken-ichi、Suzuki Yutaka、Matsumoto Masaki、Nakayama Keiichi I.、Hirayama Akiyoshi、Soga Tomoyoshi、Kuroda Shinya
    • Journal Title

      iScience

      Volume: 25 Issue: 2 Pages: 103787-103787

    • DOI

      10.1016/j.isci.2022.103787

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Trans-omic analysis of hepatic glucose metabolism and its dysfunction associated with obesity(トランスオミクスによる肥満に伴う肝臓での代謝応答システムの破綻)2025

    • Author(s)
      黒田 真也
    • Organizer
      APPW2025 第130回日本解剖学会/第102回日本生理学会/第98回日本薬理学会合同大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Trans-omic analysis of glucose metabolism and its dysfunction associated with obesity2024

    • Author(s)
      Shinya Kuroda
    • Organizer
      International Conference Systems Biology (ICSB) 2024
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] トランスオミクスによる肝臓での糖応答代謝システムの解析2024

    • Author(s)
      黒田 真也
    • Organizer
      第18回メタボロームシンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Metabolome Analysis in Mice Liver Using Thermodynamics2024

    • Author(s)
      Takumi Abekawa, Satoshi Ohno, Shinya Kuroda
    • Organizer
      第21回国際生物物理会議
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transomic network analysis of glucose metabolism and its dysfunction associated with obesity2023

    • Author(s)
      Shinya Kuroda
    • Organizer
      5th MHRC symposium at SIMS
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] トランスオミクスによる肝臓での糖応答システムの解析2023

    • Author(s)
      黒田 真也
    • Organizer
      東海糖尿病代謝連携懇話会学術講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] トランスオミクスによる肝臓での糖応答システムの解析2023

    • Author(s)
      黒田 真也
    • Organizer
      第30回 日本遺伝子診療学会大会・第8回クリニカルバイオバンク学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Kinetic transomic analysis reveals time- and dose-dependent selective glucose metabolism for glucose homeostasis and energy conversion in the liver2023

    • Author(s)
      Yifei Pan , Atsushi Hatano , Satoshi Ohno , Keigo Morita , Toshiya Kokaji , Atsushi J. Nagano ,Akiyoshi Hirayama , Tomoyoshi Soga and Shinya Kuroda
    • Organizer
      ICSB 2023(The 22nd International Conference on Systems Biology)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity2023

    • Author(s)
      Yunfan Bai, Keigo Morita, Toshiya Kokaji, Akiyoshi Hirayama, Tomoyoshi Soga and Shinya Kuroda
    • Organizer
      ICSB 2023(The 22nd International Conference on Systems Biology)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transomic network analysis of glucose metabolism and its dysfunction associated with obesity2022

    • Author(s)
      Shinya Kuroda
    • Organizer
      The 21th International Conference on Systems Biology (ICSB) 2022
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The roles of inter- and intra-cellular variations in cellular information transfer2022

    • Author(s)
      Shinya Kuroda
    • Organizer
      Workshop on Non-equilibrium Phenomena in Physics and Biology (NE-PB2022)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Systems Biology of Insulin Action2022

    • Author(s)
      Shinya Kuroda
    • Organizer
      Biomedical Mathematics Online Colloquium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ストラクチャオーム/ structurome オミクスワイドのタンパク質立体構造(ストラクチャオーム)に向けて Toward an omics-wide protein structure (structurome)2022

    • Author(s)
      黒田 真也
    • Organizer
      第45回 日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 骨格筋のシステムバイオロジー:代謝トランスオミクスと情報誌論解析2022

    • Author(s)
      黒田 真也
    • Organizer
      第9回骨格筋生物学研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] インスリン作用のトランスオミクスネットワーク2021

    • Author(s)
      黒田 真也
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] トランスオミクスによる肝臓での糖応答システムの解析2021

    • Author(s)
      黒田 真也
    • Organizer
      第94回日本内分泌学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Book] 実験医学Vol.43 No.4:トランスオミクスネットワークを構築・解析するウェブツール「iTraNet」2025

    • Author(s)
      杉本光、黒田真也
    • Publisher
      羊土社
    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2026-01-16  

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