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Modelling the generation of the epithelial cells in the small intestinal crypt

Reference	BBS/E/F/00044451
Principal Investigator / Supervisor	Dr Maria Pin Arias
Co-Investigators / Co-Supervisors
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	35,400
Status	Completed
Type	Institute Project
Start date	01/04/2010
End date	31/03/2012
Duration	24 months

Abstract

The intestinal epithelium lining the GI tract is folded to form a number of invaginations or crypts. In the small intestine, several crypts surround the base of finger-like luminal projections called villi. The epithelial renewal is driven by stem cells located at the bottom of the intestinal crypt. Epithelial cells produced in the lower part of the crypt migrate upward along the axis of adjacent villus and simultaneously proliferate and differentiate into three functional types: absorptive cells or enterocytes, mucus-secreting Goblet cells and enteroendocrine cells. A fourth differentiated type cell, the Paneth cell, have been assumed to migrate downward populating the crypt base in the small intestine. Cell differentiation in the crypt is driven by complex cellular signalling pathways. Long-term DNA labelling retention is a stem cell feature identified in cells located just above the Paneth cell compartment at position +4. The Lgr5 stem cell marker has been observed in these cells located in +4 position but also and with higher intensity in cells located between Paneth cells at the crypt base. Sorted high intensity Lgr5 positive cells can form crypt–villus organoids with all epithelial cell types in culture. A novel approach for modelling the GI system is based in constructing an individual cell model in the spatial representation of the major features of the GI tract environment. Features and dynamics of individual cells are stochastically modelled in time. Simulations of the emerging stochastic system are validated with experimental data. The integration of experimental data with this modelling approach aims to uncover the potential mechanisms behind various events such as cell proliferation, differentiation and migration and signalling processes.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Stem Cells, Systems Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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