title: A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types.
abstract: Models of the development and early progression of colorectal cancer are based upon understanding the cycle of stem cell turnover, proliferation, differentiation and death. Existing crypt compartmental models feature a linear pathway of cell types, with little regulatory mechanism. Previous work has shown that there are perturbations in the enteroendocrine cell population of macroscopically normal crypts, a compartment not included in existing models. We show that existing models do not adequately recapitulate the dynamics of cell fate pathways in the crypt. We report the progressive development, iterative testing and fitting of a developed compartmental model with additional cell types, and which includes feedback mechanisms and cross-regulatory mechanisms between cell types. The fitting of the model to existing data sets suggests a need to invoke cross-talk between cell types as a feature of colon crypt cycle models.
authors.affiliation: Manchester Centre for Integrative Systems Biology, University of Manchester, Manchester, UK.
authors.forename: Kieran
authors.initials: K
authors.lastname: Smallbone
authors.forename: Bernard
authors.initials: B
authors.lastname: M Corfe
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D003106:Colon / Q000473:pathology* / Q000503:physiopathology; D015179:Colorectal Neoplasms / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D019858:Enteroendocrine Cells / Q000473:pathology* / Q000502:physiology; D006801:Humans; D008962:Models, Theoretical; D013234:Stem Cells / Q000473:pathology* / Q000502:physiology
keywords: apoptosis; cancer; cell cycle; cell-cell signalling; colon crypt; differentiation; mathematical model