Modeling of stem cell dynamics in human colonic crypts in silico

Yuki Kagawa, Noriko Horita, Hideki Taniguchi, Satoshi Tsuneda

    研究成果: Article

    9 引用 (Scopus)

    抄録

    Background: Several possible scenarios of cellular dynamics in human colonic crypts have been inferred from transgenic animal experiments. However, because of the discrepancy in size and physiology between humans and animals, quantitative predictions of tissue renewal and cancer development are difficult to execute. Methods: A two-dimensional individual based model was developed for the first time to predict cellular dynamics in human colonic crypts. A simple scenario, in which stem cells were not fixed positionally, divide symmetrically and asymmetrically in a stochastic fashion in the lower part of the crypt, was proposed and implemented in the developed model. Numerical simulations of the model were executed in silico. Results: By comparing the results of computational simulations with available experimental data, the presented scenario was consistent with various experimental evidence. Using this scenario, we simulated and visualized monoclonal conversion in the human colonic crypt. We also predicted that the propensity for monoclonal expansion of a mutant cell was largely dependent on the phenotype, the cell type, the position and the state of the crypt. Conclusions: Using the computational framework developed in this study, model users can verify possible scenarios of stem cell dynamics occurring in human colonic crypts and quantitatively predict cell behavior. Its applicability in scenario verification and predictability makes it a valuable tool for elucidation of stem cell dynamics in human colonic crypts.

    元の言語English
    ページ(範囲)263-269
    ページ数7
    ジャーナルJournal of Gastroenterology
    49
    発行部数2
    DOI
    出版物ステータスPublished - 2014 2

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    Computer Simulation
    Stem Cells
    Genetically Modified Animals
    Phenotype
    Neoplasms

    ASJC Scopus subject areas

    • Gastroenterology

    これを引用

    Modeling of stem cell dynamics in human colonic crypts in silico. / Kagawa, Yuki; Horita, Noriko; Taniguchi, Hideki; Tsuneda, Satoshi.

    :: Journal of Gastroenterology, 巻 49, 番号 2, 02.2014, p. 263-269.

    研究成果: Article

    Kagawa, Yuki ; Horita, Noriko ; Taniguchi, Hideki ; Tsuneda, Satoshi. / Modeling of stem cell dynamics in human colonic crypts in silico. :: Journal of Gastroenterology. 2014 ; 巻 49, 番号 2. pp. 263-269.
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    abstract = "Background: Several possible scenarios of cellular dynamics in human colonic crypts have been inferred from transgenic animal experiments. However, because of the discrepancy in size and physiology between humans and animals, quantitative predictions of tissue renewal and cancer development are difficult to execute. Methods: A two-dimensional individual based model was developed for the first time to predict cellular dynamics in human colonic crypts. A simple scenario, in which stem cells were not fixed positionally, divide symmetrically and asymmetrically in a stochastic fashion in the lower part of the crypt, was proposed and implemented in the developed model. Numerical simulations of the model were executed in silico. Results: By comparing the results of computational simulations with available experimental data, the presented scenario was consistent with various experimental evidence. Using this scenario, we simulated and visualized monoclonal conversion in the human colonic crypt. We also predicted that the propensity for monoclonal expansion of a mutant cell was largely dependent on the phenotype, the cell type, the position and the state of the crypt. Conclusions: Using the computational framework developed in this study, model users can verify possible scenarios of stem cell dynamics occurring in human colonic crypts and quantitatively predict cell behavior. Its applicability in scenario verification and predictability makes it a valuable tool for elucidation of stem cell dynamics in human colonic crypts.",
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    AB - Background: Several possible scenarios of cellular dynamics in human colonic crypts have been inferred from transgenic animal experiments. However, because of the discrepancy in size and physiology between humans and animals, quantitative predictions of tissue renewal and cancer development are difficult to execute. Methods: A two-dimensional individual based model was developed for the first time to predict cellular dynamics in human colonic crypts. A simple scenario, in which stem cells were not fixed positionally, divide symmetrically and asymmetrically in a stochastic fashion in the lower part of the crypt, was proposed and implemented in the developed model. Numerical simulations of the model were executed in silico. Results: By comparing the results of computational simulations with available experimental data, the presented scenario was consistent with various experimental evidence. Using this scenario, we simulated and visualized monoclonal conversion in the human colonic crypt. We also predicted that the propensity for monoclonal expansion of a mutant cell was largely dependent on the phenotype, the cell type, the position and the state of the crypt. Conclusions: Using the computational framework developed in this study, model users can verify possible scenarios of stem cell dynamics occurring in human colonic crypts and quantitatively predict cell behavior. Its applicability in scenario verification and predictability makes it a valuable tool for elucidation of stem cell dynamics in human colonic crypts.

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    KW - Monoclonal conversion

    KW - Mutation accumulation

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