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.
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.
Authors: Tariq G Fellous; Stuart A C McDonald; Julia Burkert; Adam Humphries; Shahriar Islam; Nemantha M W De-Alwis; Lydia Gutierrez-Gonzalez; Paul J Tadrous; George Elia; Hemant M Kocher; Satyajit Bhattacharya; Lisa Mears; Mona El-Bahrawy; Douglas M Turnbull; Robert W Taylor; Laura C Greaves; Patrick F Chinnery; Christopher P Day; Nicholas A Wright; Malcolm R Alison Journal: Stem Cells Date: 2009-06 Impact factor: 6.277
Authors: Emina H Huang; Mark J Hynes; Tao Zhang; Christophe Ginestier; Gabriela Dontu; Henry Appelman; Jeremy Z Fields; Max S Wicha; Bruce M Boman Journal: Cancer Res Date: 2009-03-31 Impact factor: 12.701
Authors: Nick Barker; Johan H van Es; Jeroen Kuipers; Pekka Kujala; Maaike van den Born; Miranda Cozijnsen; Andrea Haegebarth; Jeroen Korving; Harry Begthel; Peter J Peters; Hans Clevers Journal: Nature Date: 2007-10-14 Impact factor: 49.962