Dataset Information

Smallbone2013 - Colon Crypt cycle - Version 1

ABSTRACT: Smallbone2013 - Colon Crypt cycle - Version 1 This model is described in the article: A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types Kieran Smallbone, Bernard M. Corfe Int J Exp Pathol. 2014 Feb;95(1):1-7. 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. This model is hosted on BioModels Database and identified by: MODEL1306190001 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Kieran Smallbone

PROVIDER: BIOMD0000000519 | BioModels | 2011-12-01

REPOSITORIES: BioModels

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Publications

A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types.

Smallbone Kieran K M Corfe Bernard B

International journal of experimental pathology 20131220 1

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 adequate ...[more]

PMID: 24354351

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Project description:Smallbone2013 - Colon Crypt cycle - Version 0 This model is described in the article: A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types Kieran Smallbone, Bernard M. Corfe Int J Exp Pathol. 2014 Feb;95(1):1-7. 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. This model is hosted on BioModels Database and identified by: MODEL1306190000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Smallbone2013 - Colon Crypt cycle - Version 2 This model is described in the article: A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types Kieran Smallbone, Bernard M. Corfe Int J Exp Pathol. 2014 Feb;95(1):1-7. 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. This model is hosted on BioModels Database and identified by: MODEL1306190002 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Smallbone2013 - Colon Crypt cycle - Version 3 This model is described in the article: A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types Kieran Smallbone, Bernard M. Corfe Int J Exp Pathol. 2014 Feb;95(1):1-7. 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. This model is hosted on BioModels Database and identified by: MODEL1306190003 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Background & Aims: HNF4Î± is an important transcriptional regulator of hepatocyte and pancreatic function. Hnf4Î± deletion is embryonically lethal with severe defects in visceral endoderm formation, liver maturation and colon development. However, the precise role of this transcription factor in maintaining homeostasis of the adult intestine remains unclear. Herein, we aimed to elucidate the adult intestinal functions of Hnf4Î±. Methods: A conditional intestinal epithelial Hnf4Î± knockout mouse was generated. Histological abnormality of the colonic mucosa was assessed by immunodetection and Western. Changes in global gene expression and biological network were analyzed. Results: Hnf4Î± intestine null mice developed normally until reaching young adulthood. Crypt distortion became apparent in the Hnf4Î± null colon at 3 months of age followed by focal areas of crypt dropout, increased immune cell infiltrates, crypt hyperplasia and early signs of polyposis later in life. A gene profiling analysis identified cell death and cell cycle related to cancer as the most significant sets of genes altered in the Hnf4Î± colon null mice. Expression levels of the tight junction proteins claudin 4, 8 and 15 were altered early in the colon epithelium of Hnf4Î± mutants and correlated with increased barrier permeability to a molecular tracer that does not normally penetrate normal mucosa. Conclusion: These observations support a functional role for Hnf4Î± in protecting the colonic mucosa against the initiation of the changes resembling inflammatory bowel diseases and polyp formation. Experiment Overall Design: HNF4alpha was conditionally knockout in the mouse epithelial colon with the villin CRE. A total of 3 control and 3 mutant littermates individuals were sacrificed at 1 year of age. The colon was harvested and Total RNA was isolated from each individuals. Each RNA sample was independently used to generate probes to screen affymetrix chips.

Dataset Information

Smallbone2013 - Colon Crypt cycle - Version 1

Publications

A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types.

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