a two-dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath的二维模型结肠隐窝占基底膜的作用和pericryptal纤维母细胞鞘.pdfVIP
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a two-dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath的二维模型结肠隐窝占基底膜的作用和pericryptal纤维母细胞鞘
A Two-Dimensional Model of the Colonic Crypt
Accounting for the Role of the Basement Membrane and
Pericryptal Fibroblast Sheath
1,2 3 3 ¨ 3 1,4
Sara-Jane Dunn *, Paul L. Appleton , Scott A. Nelson , Inke S. Nathke , David J. Gavaghan ,
James M. Osborne1,4
1 Department of Computer Science, University of Oxford, Oxford, United Kingdom, 2 Microsoft Research Ltd., Cambridge, United Kingdom, 3 College of Life Sciences,
University of Dundee, Dundee, United Kingdom, 4 Oxford Centre for Integrative Systems Biology, Department of Biochemistry, Oxford, United Kingdom
Abstract
The role of the basement membrane is vital in maintaining the integrity and structure of an epithelial layer, acting as both a
mechanical support and forming the physical interface between epithelial cells and the surrounding connective tissue. The
function of this membrane is explored here in the context of the epithelial monolayer that lines the colonic crypt, test-tube
shaped invaginations that punctuate the lining of the intestine and coordinate a regular turnover of cells to replenish the
epithelial layer every few days. To investigate the consequence of genetic mutations that perturb the system dynamics and
can lead to colorectal cancer, it must be possible to track the emerging tissue level changes that arise in the crypt. To that
end, a theoretical crypt model with a realistic, deformable geometry is required. A new discrete crypt model is presented,
which focuses on the interaction between cell- and tissue-level behaviour, while incorporating key subcellular components.
The model contains a novel description of the role of the surrounding tissue and musculature, based upon experimental
observations of the tissue structure of the
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