九州大学 研究者情報
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基本情報 研究活動 教育活動 社会活動
三浦 岳(みうら たかし) データ更新日:2021.07.01

教授 /  医学研究院 基礎医学部門 生体制御学講座 系統解剖学分野


主な研究テーマ
生物のパターン形成の数理モデル化とその実験的検証
キーワード:パターン形成 数理モデル 反応拡散 粒子多体系 発生生物学
1996.04~2013.02.
従事しているプロジェクト研究
生理学と協働した数理科学による皮膚疾患機構の解明
2010.04~2015.03, 代表者:長山雅晴, 北海道大学, 北海道大学.
研究業績
主要著書
主要原著論文
1. Kei Sugihara, Saori Sasaki, Akiyoshi Uemura, Satoru Kidoaki, Takashi Miura, Mechanisms of endothelial cell coverage by pericytes: computational modelling of cell wrapping and in vitro experiments, Journal of The Royal Society Interface, 10.1098/rsif.2019.0739, 17, 162, 20190739-20190739, 2020.01, Pericytes (PCs) wrap around endothelial cells (ECs) and perform diverse functions in physiological and pathological processes. Although molecular interactions between ECs and PCs have been extensively studied, the morphological processes at the cellular level and their underlying mechanisms have remained elusive. In this study, using a simple cellular Potts model, we explored the mechanisms for EC wrapping by PCs. Based on the observed
in vitro
cell wrapping in three-dimensional PC–EC coculture, the model identified four putative contributing factors: preferential adhesion of PCs to the extracellular matrix (ECM), strong cell–cell adhesion, PC surface softness and larger PC size. While cell–cell adhesion can contribute to the prevention of cell segregation and the degree of cell wrapping, it cannot determine the orientation of cell wrapping alone. While atomic force microscopy revealed that PCs have a larger Young’s modulus than ECs, the experimental analyses supported preferential ECM adhesion and size asymmetry. We also formulated the corresponding energy minimization problem and numerically solved this problem for specific cases. These results give biological insights into the role of PC–ECM adhesion in PC coverage. The modelling framework presented here should also be applicable to other cell wrapping phenomena observed
in vivo
..
2. Yuji Nashimoto, Tomoya Hayashi, Itsuki Kunita, Akiko Nakamasu, Yu-Suke Torisawa, Masamune Nakayama, Hisako Takigawa-Imamura, Hidetoshi Kotera, Koichi Nishiyama, Takashi Miura, Ryuji Yokokawa, Integrating perfusable vascular networks with a three-dimensional tissue in a microfluidic device., Integrative biology : quantitative biosciences from nano to macro, 10.1039/c7ib00024c, 9, 6, 506-518, 2017.06, Creating vascular networks in tissues is crucial for tissue engineering. Although recent studies have demonstrated the formation of vessel-like structures in a tissue model, long-term culture is still challenging due to the lack of active perfusion in vascular networks. Here, we present a method to create a three-dimensional cellular spheroid with a perfusable vascular network in a microfluidic device. By the definition of the cellular interaction between human lung fibroblasts (hLFs) in a spheroid and human umbilical vein endothelial cells (HUVECs) in microchannels, angiogenic sprouts were induced from microchannels toward the spheroid; the sprouts reached the vessel-like structures in a spheroid to form a continuous lumen. We demonstrated that the vascular network could administer biological substances to the interior of the spheroid. As cell density in the spheroid is similar to that of a tissue, the perfusable vasculature model opens up new possibilities for a long-term tissue culture in vitro..
3. Takumi Higaki, Hisako Takigawa-Imamura, Kae Akita, Natsumaro Kutsuna, Ryo Kobayashi, Seiichiro Hasezawa, Takashi Miura, Exogenous Cellulase Switches Cell Interdigitation to Cell Elongation in an RIC1-dependent Manner in Arabidopsis thaliana Cotyledon Pavement Cells, Plant and Cell Physiology, 10.1093/pcp/pcw183, pcw183-pcw183, 2016.12.
4. Takumi Higaki, Natsumaro Kutsuna, Kae Akita, Hisako Takigawa-Imamura, Kenji Yoshimura, Takashi Miura, A Theoretical Model of Jigsaw-Puzzle Pattern Formation by Plant Leaf Epidermal Cells, PLOS COMPUTATIONAL BIOLOGY, 10.1371/journal.pcbi.1004833, 12, 4, e1004833, 2016.04, Plant leaf epidermal cells exhibit a jigsaw puzzle-like pattern that is generated by interdigitation of the cell wall during leaf development. The contribution of two ROP GTPases, ROP2 and ROP6, to the cytoskeletal dynamics that regulate epidermal cell wall interdigitation has already been examined; however, how interactions between these molecules result in pattern formation remains to be elucidated. Here, we propose a simple interface equation model that incorporates both the cell wall remodeling activity of ROP GTPases and the diffusible signaling molecules by which they are regulated. This model successfully reproduces pattern formation observed in vivo, and explains the counterintuitive experimental results of decreased cellulose production and increased thickness. Our model also reproduces the dynamics of three-way cell wall junctions. Therefore, this model provides a possible mechanism for cell wall interdigitation formation in vivo..
5. Alvaro Köhn-Luque, Walter de Back, Yoshimi Yamaguchi, Kenji Yoshimura, Miguel A Herrero, Takashi Miura, Dynamics of VEGF matrix-retention in vascular network patterning, Physical Biology, 10.1088/1478-3975/10/6/066007, 10, 6, 066007-066007, 2013.12.
6. Shigeru Kondo, Takashi Miura, Reaction-Diffusion Model as a Framework for Understanding Biological Pattern Formation, Science, 10.1126/science.1179047, 329, 5999, 1616-1620, 2010.09.
7. Takashi Miura, Chad A. Perlyn, Masato Kinboshi, Naomichi Ogihara, Mikiko Kobayashi-Miura, Gillian M. Morriss-Kay, Kohei Shiota, Mechanism of skull suture maintenance and interdigitation, Journal of Anatomy, 10.1111/j.1469-7580.2009.01148.x, 215, 6, 642-655, 2009.12.
8. Miura, T., Hartmann, D., Kinboshi, M., Komada, M., Ishibashi, M., Shiota, K., The cyst-branch difference in developing chick lung results from a different morphogen diffusion coefficient, Mechanisms of Development, 10.1016/j.mod.2008.11.006, 126, 3-4, 160-172, 2009.04, The developing avian lung is formed mainly by branching morphogenesis, but there is also a unique cystic structure, the air sac, in the ventral region. It has been shown that mesenchymal tissue is responsible for the differential development of a cystic or branched structure, and that the transcription factor Hoxb may be involved in determining this regional difference. We have previously developed two scenarios for branch-cyst transition, both experimentally and theoretically: increased production or increased diffusion of FGF. The aim of the present study was to discover whether one of these scenarios actually operates in the ventral region of the chick lung. We found that the FGF10 level was lower while the diffusion of FGF10 was more rapid in the ventral lung, indicating that the second scenario is more plausible. There are two possibilities as to why the diffusion of FGF10 differs between the two regions: (1) diffusion is facilitated by the looser tissue organisation of the ventral lung mesenchyme; (2) stronger expression of heparan sulphate proteoglycan ( HSPG) in the dorsal lung traps FGF and decreases the effective diffusion coefficient. Mathematical analysis showed that the dorsal-ventral difference in the amount of HSPG is not sufficient to generate the observed difference in pattern, indicating that both extracellular matrix and tissue architecture play a role in this system. These results suggest that the regional cystic-branched difference within the developing chick lung results from a difference in the rate of diffusion of morphogen between the ventral and dorsal regions due to differential levels of HSPG and a different mesenchymal structure. (C) 2008 Elsevier Ireland Ltd. All rights reserved..
9. Dirk Hartmann, Takashi Miura, Modelling in vitro lung branching morphogenesis during development, Journal of Theoretical Biology, 10.1016/j.jtbi.2006.05.009, 242, 4, 862-872, 2006.10.
10. Takashi Miura, Kohei Shiota, Gillian Morriss-Kay, Philip K. Maini, Mixed-mode pattern in Doublefoot mutant mouse limb—Turing reaction–diffusion model on a growing domain during limb development, Journal of Theoretical Biology, 10.1016/j.jtbi.2005.10.016, 240, 4, 562-573, 2006.06.
11. Takashi Miura, Philip K. Maini, Speed of pattern appearance in reaction-diffusion models: implications in the pattern formation of limb bud mesenchyme cells, Bulletin of Mathematical Biology, 10.1016/j.bulm.2003.09.009, 66, 4, 627-649, 2004.07.
12. Takashi Miura, Kohei Shiota, Depletion of FGF acts as a lateral inhibitory factor in lung branching morphogenesis in vitro, Mechanisms of Development, 10.1016/s0925-4773(02)00132-6, 116, 1-2, 29-38, 2002.08.
13. Takashi Miura, Kohei Shiota, TGFβ2 acts as an 'activator' molecule in reaction-diffusion model and is involved in cell sorting phenomenon in mouse limb micromass culture, Developmental Dynamics, 10.1002/(SICI)1097-0177(200003)217:3<241::AID-DVDY2>3.0.CO;2-K, 217, 3, 241-249, 2000.04, It was previously speculated that TGFβ acts as an 'activator'-molecule in chondrogenic pattern formation in the limb micromass culture system, but its precise role and relationship with the cell sorting phenomenon have not been properly studied. In the present study, we examined whether the TGFβ2 molecule satisfies the necessary conditions for an 'activator'-molecule in the reaction-diffusion model. Firstly, we showed that TGFβ2 became localized at chondrogenic sites during the establishment of a chondrogenic pattern, and exogenous TGFβ2 promoted chondrogenesis when added in the culture medium. Secondly, TGFβ2 protein was shown to promote the production of its own mRNA after 3 hr, indicating that a positive feedback mechanism exists which may be responsible for the emergence of the chondrogenic pattern. We then found that when locally applied with beads, TGFβ2 suppressed chondrogenesis around the beads, indicating it induces the lateral inhibitory mechanism, which is a key element for the formation of the periodic pattern. We also examined the possible effects of TGFβ2 on the cell sorting phenomenon and found that TGFβ2 exerts differential chemotactic activity on proximal and distal mesenchyme cells of the limb bud, and at very early phases of differentiation TGFβ2 promotes the expression of N-cadherin protein which is known to be involved in pattern formation in this culture system. These findings suggest that TGFβ2 acts as an 'activator'-like molecule in chondrogenic pattern formation in vitro, and is possibly responsible for the cell sorting phenomenon. (C) 2000 Wiley- Liss, Inc..
主要総説, 論評, 解説, 書評, 報告書等
主要学会発表等
学会活動
所属学会名
解剖学会
発生生物学会
先天異常学会
生物物理学会
数理生物学会
数理生物学会
Society for Developmental Biologists
先天異常学会
解剖学会
発生生物学会
学会大会・会議・シンポジウム等における役割
2016.09.07~2016.09.09, 日本数理生物学会, シンポジウム主催.
学術論文等の審査
年度 外国語雑誌査読論文数 日本語雑誌査読論文数 国際会議録査読論文数 国内会議録査読論文数 合計
2013年度    
2014年度      
2015年度 11        11 
2016年度      
2017年度      
2018年度 10        10 
2019年度      
2020年度      
その他の研究活動
海外渡航状況, 海外での教育研究歴
Univ Compultense de Madrid, EMBL Heidelberg, Spain, Germany, 2011.12~2011.12.
Oxford University, Heidelberg University, UnitedKingdom, Germany, 2002.07~2004.06.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2015年度~2018年度, 基盤研究(B), 発生におけるマルチスケールの自発的パターン形成現象の数理の解明.
2016年度~2018年度, 基盤研究(C), 植物オルガネラの統合的フェノーム解析技術の研究.
2016年度~2017年度, 基盤研究(C), 網膜新生血管における内皮細胞ダイナミクスの解析.
2015年度~2016年度, 基盤研究(C), 葉表皮細胞の人為的変形系を用いた細胞形態および細胞間信号伝達シミュレーション解析.
2014年度~2016年度, 基盤研究(C), 植物表皮細胞壁のジグソーパズル構造形成メカニズム.
2012年度~2016年度, 基盤研究(C), 細胞骨格の制御を介した細胞外情報処理機構の解明.
2014年度~2015年度, 基盤研究(C), 自己組織化を利用したオンチップ血管モデルの開発―血管生理・病態の再現と理解.
2013年度~2015年度, 基盤研究(C), RhoJによる内皮細胞運動と血管網パターン形成の制御機構.
2013年度~2015年度, 基盤研究(C), 形態形成理解のためのマルチスケールマウス初期胚培養デバイス.
2013年度~2014年度, 基盤研究(C), 被毛パターン変異ラットを用いた反応拡散モデル実証のための実験モデル系の創出.
2013年度~2013年度, 基盤研究(C), 代表, 発生に於けるパターン形成現象の 数理モデル化.
2011年度~2012年度, 基盤研究(C), 生物の形作りの数理的記述法の確立.
2011年度~2012年度, 基盤研究(C), 肺の枝分かれ構造形成における細胞集団運動のメカニズムの解明.
2010年度~2012年度, 基盤研究(C), 発生過程の関節軟骨の力学特性とリハビリテーションの基礎的研究.
2010年度~2012年度, 基盤研究(C), 頭蓋骨縫合線のパターン形成の数理モデル化とその実験的検証.
2008年度~2010年度, 基盤研究(C), 前脳形態形成におけるシグナル分子の役割の解明.
2007年度~2010年度, 基盤研究(C), 代表, 上皮組織のかたちづくりを理解する.
2007年度~2010年度, 基盤研究(C), 生物における構造形成と情報に関する数理的研究.
2008年度~2009年度, 基盤研究(C), モルフォゲンの濃度勾配ロバストネス保証および分化運命決定における閾値の分子機構.
2006年度~2007年度, 基盤研究(C), 前脳形態形成分子機構の解明.
2005年度~2007年度, 基盤研究(C), 哺乳動物の発生過程における自発的パターン形成現象の数理モデル化とその実験的検証.
2002年度~2004年度, 基盤研究(C), 内耳原基の器官培養系を用いた内耳の形態形成機構と内耳奇形発生のメカニズムの解明.
2001年度~2002年度, 基盤研究(C), マウス胎児肢芽細胞の微少集積培養系におけるパターン形成メカニズムの解明.
2000年度~2001年度, 基盤研究(C), 胎児の肺原基における初期分枝パターンの数理モデル化とその実験的検証.
1998年度~1999年度, 特別研究員奨励費, 代表, 哺乳類の形態形成現象に関与する分子の三次元的定量とその数理モデル化の研究.
競争的資金(受託研究を含む)の採択状況
2014年度~2014年度, 上原記念財団研究推進特別奨励金, 代表, 発生に於けるパターン形成現象の数理モデル化.

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