Document Detail

Cell differentiation modeled via a coupled two-switch regulatory network.
MedLine Citation:
PMID:  21198133     Owner:  NLM     Status:  In-Process    
Mesenchymal stem cells can give rise to bone and other tissue cells, but their differentiation still escapes full control. In this paper we address this issue by mathematical modeling. We present a model for a genetic switch determining the cell fate of progenitor cells which can differentiate into osteoblasts (bone cells) or chondrocytes (cartilage cells). The model consists of two switch mechanisms and reproduces the experimentally observed three stable equilibrium states: a progenitor, an osteogenic, and a chondrogenic state. Conventionally, the loss of an intermediate (progenitor) state and the entailed attraction to one of two opposite (differentiated) states is modeled as a result of changing parameters. In our model in contrast, we achieve this by distributing the differentiation process to two functional switch parts acting in concert: one triggering differentiation and the other determining cell fate. Via stability and bifurcation analysis, we investigate the effects of biochemical stimuli associated with different system inputs. We employ our model to generate differentiation scenarios on the single cell as well as on the cell population level. The single cell scenarios allow to reconstruct the switching upon extrinsic signals, whereas the cell population scenarios provide a framework to identify the impact of intrinsic properties and the limiting factors for successful differentiation.
D Schittler; J Hasenauer; F Allgöwer; S Waldherr
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chaos (Woodbury, N.Y.)     Volume:  20     ISSN:  1089-7682     ISO Abbreviation:  Chaos     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-01-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100971574     Medline TA:  Chaos     Country:  United States    
Other Details:
Languages:  eng     Pagination:  045121     Citation Subset:  IM    
Copyright Information:
© 2010 American Institute of Physics.
Institute for Systems Theory and Automatic Control, University of Stuttgart, 70550 Stuttgart, Germany.
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