Document Detail

An integrated systems biology approach to understanding the rules of keratinocyte colony formation.
MedLine Citation:
PMID:  17374590     Owner:  NLM     Status:  MEDLINE    
Closely coupled in vitro and in virtuo models have been used to explore the self-organization of normal human keratinocytes (NHK). Although it can be observed experimentally, we lack the tools to explore many biological rules that govern NHK self-organization. An agent-based computational model was developed, based on rules derived from literature, which predicts the dynamic multicellular morphogenesis of NHK and of a keratinocyte cell line (HaCat cells) under varying extracellular Ca++ concentrations. The model enables in virtuo exploration of the relative importance of biological rules and was used to test hypotheses in virtuo which were subsequently examined in vitro. Results indicated that cell-cell and cell-substrate adhesions were critically important to NHK self-organization. In contrast, cell cycle length and the number of divisions that transit-amplifying cells could undergo proved non-critical to the final organization. Two further hypotheses, to explain the growth behaviour of HaCat cells, were explored in virtuo-an inability to differentiate and a differing sensitivity to extracellular calcium. In vitro experimentation provided some support for both hypotheses. For NHKs, the prediction was made that the position of stem cells would influence the pattern of cell migration post-wounding. This was then confirmed experimentally using a scratch wound model.
Tao Sun; Phil McMinn; Simon Coakley; Mike Holcombe; Rod Smallwood; Sheila Macneil
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the Royal Society, Interface / the Royal Society     Volume:  4     ISSN:  1742-5689     ISO Abbreviation:  J R Soc Interface     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-10-19     Completed Date:  2008-01-18     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  101217269     Medline TA:  J R Soc Interface     Country:  England    
Other Details:
Languages:  eng     Pagination:  1077-92     Citation Subset:  IM    
Department of Engineering Materials, University of Sheffield, Kroto Research Institute, Sheffield, UK.
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MeSH Terms
Cell Differentiation
Cell Division
Cell Line
Computer Simulation
Keratinocytes / cytology*,  physiology*
Models, Biological*
Stem Cells / cytology,  physiology
Systems Biology*

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