• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

3D morphogenesis of epithelial cell sheets in vitro

Planned Research

Project AreaDiscovery of the logic that establishes the 3D structure of organisms
Project/Area Number 15H05858
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHokkaido University

Principal Investigator

Haga Hisashi  北海道大学, 先端生命科学研究院, 教授 (00292045)

Co-Investigator(Kenkyū-buntansha) 石原 誠一郎  北海道大学, 先端生命科学研究院, 助教 (10719933)
古澤 和也  北海道大学, 先端生命科学研究院, 助教 (00510017)
Project Period (FY) 2015-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥85,540,000 (Direct Cost: ¥65,800,000、Indirect Cost: ¥19,740,000)
Fiscal Year 2019: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2018: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2017: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2015: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Keywords細胞・組織 / 上皮細胞シート / ゲル基質 / アクトミオシン / 集団運動 / 粘弾性基質 / ゾル基質
Outline of Final Research Achievements

Three-dimensional morphogenesis of epithelial cells plays pivotal roles in many biological events as it is observed in embryogenesis. Mechanical properties of the extracellular substrate such as viscoelasticity and geometrical constraints are known as crucial factors that affect 3D morphogenesis of epithelial sheets. In this study, we found that epithelial cells (MDCK cells) cultured on a Matrigel crosslinked by Genipin exhibit dome formation by both the swelling of extracellular matrix and aquaporin water transport triggered by the basal hypertonic stress. Computer simulation was conducted and revealed that uneven swelling with a positive feedback between extending cell and enhanced water transport induces the dome formation. Moreover, we succeeded to establish a novel spherical substrate for cell culture by using a gelatin gel capsule. Human dermal fibroblasts cultured on the gel capsule made wrinkle-like structures on the spherical substrate, mimicking the early embryogenesis.

Academic Significance and Societal Importance of the Research Achievements

インビトロでの実験は,原理の発見には有効であるが,観察した現象がアーティファクトである可能性がある.本研究では,消化管形成,体節形成などを観察するインビボの計画班と協調し,インビトロとインビボの現象を対比しながら研究を進めることができた.
また,3D形態が形成されるロジックを理解するためには,数理モデルが不可欠である.本研究では,3Dシミュレーションを担当する計画班と連携することで,細胞集団の回転やドーム形成の力学モデルを構築することができた.このように,インビボ,インビトロ,数理の連携によって,一見複雑に見えるインビボでの現象をシンプルな数理モデルで解明する新たなスキームが構築された.

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

    (36 results)

All 2019 2018 2017 2016 2015 Other

All Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Open Access: 11 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Int'l Joint Research: 5 results,  Invited: 10 results) Book (3 results) Remarks (5 results)

  • [Journal Article] Differential contributions of nonmuscle myosin IIA and IIB to cytokinesis in human immortalized fibroblasts2019

    • Author(s)
      Yamamoto, K., Otomo, K., Nemoto, T., Ishihara, S., Haga, H., Nagasaki, A., Murakami, Y., Takahashi, M.
    • Journal Title

      Experimental Cell Research

      Volume: 376 Issue: 1 Pages: 67-76

    • DOI

      10.1016/j.yexcr.2019.01.020

    • NAID

      120006803950

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice.2019

    • Author(s)
      Acebedo AR, Suzuki K, Hino S, Alcantara MC, Sato Y, Haga H, Matsumoto KI, Nakao M, Shimamura K, Takeo T, Nakagata N, Miyagawa S, Nishinakamura R, Adelstein RS, Yamada G.
    • Journal Title

      Commun. Biol.

      Volume: eCollection Issue: 1 Pages: 95-95

    • DOI

      10.1038/s42003-019-0336-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modulation and characterization of the double network hydrogel surface-bulk transition.2019

    • Author(s)
      Frauenlob M, King DR, Guo H, Ishihara S, Tsuda M, Kurokawa T, Haga H, Tanaka S, Gong JP.
    • Journal Title

      Macromolecules

      Volume: 52 Issue: 17 Pages: 6704-6713

    • DOI

      10.1021/acs.macromol.9b01399

    • NAID

      120006885161

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anisotropic Multi-channel Collagen Gel (MCCG) Guides the Growth Direction of the Neurite-like Processes of PC12 Cells2018

    • Author(s)
      Koh Isabel、Furusawa Kazuya、Haga Hisashi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1

    • DOI

      10.1038/s41598-018-32156-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term Culture of Human iPS Cell-derived Telencephalic Neuron Aggregates on Collagen Gel2018

    • Author(s)
      Oyama Hiroshi、Takahashi Koji、Tanaka Yoshikazu、Takemoto Hiroshi、Haga Hisashi
    • Journal Title

      Cell Structure and Function

      Volume: 43 Issue: 1 Pages: 85-94

    • DOI

      10.1247/csf.18002

    • NAID

      130006742880

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Collective Movement and 3D Morphogenesis of Epithelial Cells Induced by Softness of the Extracellular Matrix2018

    • Author(s)
      芳賀 永
    • Journal Title

      Seibutsu Butsuri

      Volume: 58 Issue: 4 Pages: 196-199

    • DOI

      10.2142/biophys.58.196

    • NAID

      130007420830

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mathematical Model of Collective Cell Migrations Based on Cell Polarity2017

    • Author(s)
      M. Akiyama, T. Sushida, S. Ishida, H. Haga
    • Journal Title

      Dev. Growth Differ

      Volume: 59 Issue: 5 Pages: 471-490

    • DOI

      10.1111/dgd.12381

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of three-dimensional culture of mouse calvaria-derived osteoblastic cells in a collagen gel with a multichannel structure on the morphogenesis behaviors of engineered bone tissues2017

    • Author(s)
      Saki Yahata, Kazuya Furusawa, Kei Nagao, Masahiro Nakajima, Toshio Fukuda
    • Journal Title

      ACS Biomaterials Science & Engineering

      Volume: 3 Issue: 12 Pages: 3414-3424

    • DOI

      10.1021/acsbiomaterials.7b00190

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anisotropic Growth of Hydroxyapatite in Stretched Double Network Hydrogel2017

    • Author(s)
      Fukao Kazuki、Nonoyama Takayuki、Kiyama Ryuji、Furusawa Kazuya、Kurokawa Takayuki、Nakajima Tasuku、Gong Jian Ping
    • Journal Title

      ACS Nano

      Volume: 11 Issue: 12 Pages: 12103-12110

    • DOI

      10.1021/acsnano.7b04942

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Data set for comparison of cellular dynamics between human AAVS1 locus-modified and wild-type cells2016

    • Author(s)
      Takeomi Mizutani, Hisashi Haga, Kazushige Kawabata
    • Journal Title

      Data in Brief

      Volume: 6 Pages: 793-798

    • DOI

      10.1016/j.dib.2015.12.053

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Conformational Plasticity of JRAB/MICAL-L2 Provides 'Law and Order'2016

    • Author(s)
      A. Sakane, S. Yoshizawa, M. Nishimura, Y. Tsuchiya, N. Matsushita, K. Miyake, K. Horikawa, I. Imoto, C. Mizuguchi, H. Saito, T. Ueno, S. Matsushita, H. Haga, S. Deguchi, K. Mizuguchi, H.
    • Journal Title

      Molecular Biology of the Cell

      Volume: 27 Issue: 20 Pages: 3095-3108

    • DOI

      10.1091/mbc.e16-05-0332

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three-dimensional morphogenesis of MDCK cells induced by cellular contractile forces on a viscous substrate2015

    • Author(s)
      Misako Imai, Kazuya Furusawa, Takeomi Mizutani, Kazushige Kawabata, Hisashi Haga
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 14208-14208

    • DOI

      10.1038/srep14208

    • NAID

      120005682122

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ゲル基質上の上皮細胞シートが引き起こす浸透圧勾配依存的なドーム形成2019

    • Author(s)
      石原(石田)すみれ、秋山 正和、須志田 隆道、古澤 和也、名黒 功、立野 浩輝、石原 誠一郎、芳賀 永
    • Organizer
      第56回 日本生化学会北海道支部例会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 球形の細胞シートでみられる細胞張力依存的な変形2019

    • Author(s)
      山村 芳央、石原 誠一郎、古澤 和也、芳賀 永
    • Organizer
      第56回 日本生化学会北海道支部例会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Osmotic stimuli triggered the dome formation of epithelial cells2019

    • Author(s)
      Sumire Ishida-Ishihara, Masakazu Akiyama, Kazuya Furusawa, Isao Naguro, Hiroki Ryuno, Takamichi Sushida, Seiichiro Ishihara, Hisashi Haga
    • Organizer
      北海道大学ライフサイエンスフォーラム 2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of collagen gels with adjustable stiffness by genipin crosslinking2019

    • Author(s)
      Haruna Kurosawa, Seiichiro Ishihara, Hisashi Haga
    • Organizer
      7th International Life-Science Symposium
    • Related Report
      2019 Annual Research Report
  • [Presentation] 浸透圧勾配が引き起こす上皮細胞シートのドーム形成2019

    • Author(s)
      石原(石田)すみれ、秋山正和、須志田隆道、古澤和也、名黒功、立野浩輝、石原誠一郎、芳賀永
    • Organizer
      日本生物物理学会北海道支部会例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Collective Movement and 3D Morphogenesis of Epithelial Cells Responding to Viscoelastic Substrates2018

    • Author(s)
      Hisashi Haga
    • Organizer
      Japan-Toronto Morphogenesis Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多細胞系のメカノバイオロジー2018

    • Author(s)
      芳賀 永
    • Organizer
      CSJ化学フェスタ
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 細胞集団に自発的な3次元形態形成を促す培養技術の開発2018

    • Author(s)
      芳賀 永,古澤 和也
    • Organizer
      帝人21世紀フォーラム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 細胞の集団運動と3次元形態形成2018

    • Author(s)
      芳賀 永
    • Organizer
      AIMaP研究会「反応拡散系と実験の融合」
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 細胞の基質牽引力と基質の粘弾性がもたらす上皮細胞の集団運動と3D形態形成2018

    • Author(s)
      芳賀 永
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Collective movement and 3D morphogenesis of epithelial cells induced by viscoelasticity of the extracellular matrix2017

    • Author(s)
      Hisashi HAGA
    • Organizer
      Japan-UCI Meeting on 3D Morphogenesis
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epithelial cell polarity essential for collective migration and 3D morphogenesis of cell sheets2017

    • Author(s)
      芳賀 永
    • Organizer
      The 18th RIES-HOKUDAI International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Construction of Engineered Bone Tissues with Complex Hierarchical Structures2017

    • Author(s)
      Kazuya Furusawa, Saki Yahata
    • Organizer
      IUMRS-ICAM 2017, The 15th International Conference on Advanced Materials
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phase Behaviors of Collagen Solution2017

    • Author(s)
      Kazuya Furusawa, Koichi Sugiyama
    • Organizer
      IUMRS-ICAM 2017, The 15th International Conference on Advanced Materials
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞外基質の粘弾性に応答する上皮細胞の集団運動と3次元形態形成2016

    • Author(s)
      芳賀 永
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば国際会議場(茨城県・つくば市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 3D morphogensis of epithelial cells responding to viscoelasticity of the extracellular matrix2016

    • Author(s)
      Hisashi Haga
    • Organizer
      Japan-Austria joint meeting "Understanding the logic behind developmental dynamics
    • Place of Presentation
      IST, Klosterneuburg(Austria)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Book] 医学のあゆみ2019

    • Author(s)
      芳賀 永
    • Total Pages
      70
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2019 Annual Research Report
  • [Book] 三次元培養における培養手法と周辺技術動向2019

    • Author(s)
      石原 誠一郎、芳賀 永
    • Total Pages
      197
    • Publisher
      情報機構
    • Related Report
      2019 Annual Research Report
  • [Book] ゲル化・増粘剤の使い方、選び方 事例集(第6章「刺激応答性」ゲルを作製するには? 第3節 異方性ゲルの作成技術)2018

    • Author(s)
      古澤 和也(分担執筆)
    • Total Pages
      691
    • Publisher
      (株)技術情報協会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 細胞ダイナミクス科学研究室

    • URL

      http://altair.sci.hokudai.ac.jp/g3

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Remarks] 細胞ダイナミクス科学研究室

    • URL

      http://altair.sci.hokudai.ac.jp/g3/

    • Related Report
      2017 Annual Research Report
  • [Remarks]

    • URL

      http://altair.sci.hokudai.ac.jp/g3/research/

    • Related Report
      2016 Annual Research Report
  • [Remarks]

    • URL

      http://www.3d-logic.jp/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 細胞ダイナミクス科学研究室 研究紹介

    • URL

      http://altair.sci.hokudai.ac.jp/g3/research/

    • Related Report
      2015 Annual Research Report

URL: 

Published: 2015-07-02   Modified: 2022-11-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi