Schittler2010 - Cell fate of progenitor cells, osteoblasts or chondrocytes

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Short description
Schittler2010 - Cell fate of progenitor cells, osteoblasts or chondrocytes

Mathematical model describing the mechanism of differentiation of mesenchymal stem cells to bone (osteoblasts) or cartilage (chondrocytes) cells.

This model is described in the article:

Schittler D, Hasenauer J, Allgöwer F, Waldherr S.
Chaos 2010 Dec; 20(4): 045121

Abstract:

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.

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.

Format
SBML (L3V1)
Related Publication
  • Cell differentiation modeled via a coupled two-switch regulatory network.
  • Schittler D, Hasenauer J, Allgöwer F, Waldherr S
  • Chaos , 12/ 2010 , Volume 20 , pages: 045121
  • Institute for Systems Theory and Automatic Control, University of Stuttgart, 70550 Stuttgart, Germany. schittler@ist.uni-stuttgart.de
  • 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.
Contributors
Steffen Waldherr, administrator

Metadata information

is
BioModels Database MODEL1310150000
BioModels Database BIOMD0000000493
isDescribedBy
PubMed 21198133
hasTaxon
Taxonomy Homo sapiens
isVersionOf
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated


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Model files

BIOMD0000000493_url.xml SBML L3V1 representation of Schittler2010 - Cell fate of progenitor cells, osteoblasts or chondrocytes 24.08 KB Preview | Download

Additional files

BIOMD0000000493-biopax2.owl Auto-generated BioPAX (Level 2) 8.11 KB Preview | Download
BIOMD0000000493.pdf Auto-generated PDF file 154.22 KB Preview | Download
BIOMD0000000493-biopax3.owl Auto-generated BioPAX (Level 3) 10.82 KB Preview | Download
BIOMD0000000493.png Auto-generated Reaction graph (PNG) 26.12 KB Preview | Download
BIOMD0000000493.svg Auto-generated Reaction graph (SVG) 10.78 KB Preview | Download
Schittler2010_Osteochondroswitch_Figure5c.xml SBML file with event assignments corresponding to Stimulus ZO, then ZD (c). 10.64 KB Preview | Download
BIOMD0000000493.xpp Auto-generated XPP file 2.73 KB Preview | Download
BIOMD0000000493_urn.xml Auto-generated SBML file with URNs 23.91 KB Preview | Download
BIOMD0000000493.sci Auto-generated Scilab file 380.00 bytes Preview | Download
Schittler2010_Osteochondroswitch_Figure5d.xml SBML file with event assignments corresponding to Stimulus ZD, then ZO; bO=0.9 (d). 10.64 KB Preview | Download
BIOMD0000000493.vcml Auto-generated VCML file 25.25 KB Preview | Download
BIOMD0000000493.m Auto-generated Octave file 4.82 KB Preview | Download
Schittler2010_Osteochondroswitch_Figure5b.xml SBML file with event assignments corresponding to Stimulus ZD, then ZO (b). 10.64 KB Preview | Download

  • Model originally submitted by : Steffen Waldherr
  • Submitted: 15-Oct-2013 08:44:29
  • Last Modified: 21-Dec-2018 17:21:52
Revisions
  • Version: 3 public model Download this version
    • Submitted on: 21-Dec-2018 17:21:52
    • Submitted by: administrator
    • With comment: Include the additional files provided by the submitter in the original submission: Schittler2010_Osteochondroswitch_Figure5b.xml, Schittler2010_Osteochondroswitch_Figure5d.xml, Schittler2010_Osteochondroswitch_Figure5c.xml
  • Version: 2 public model Download this version
    • Submitted on: 09-Oct-2014 17:40:55
    • Submitted by: Steffen Waldherr
    • With comment: Current version of Schittler2010 - Cell fate of progenitor cells, osteoblasts or chondrocytes
  • Version: 1 public model Download this version
    • Submitted on: 15-Oct-2013 08:44:29
    • Submitted by: Steffen Waldherr
    • With comment: Original import of Schittler2010_Osteochondroswitch
Curator's comment:
(added: 19 Nov 2013, 15:56:05, updated: 19 Nov 2013, 15:56:05)
Figure 5 of the reference publication has been reproduced here. The model as such reproduces figure 5a. To obtain figure 5b,c & d, the event condition for ZD and ZO has to be changed (refer figures for details). The SBML file with event assignments corresponding to figures 5b,c & d are provided as additional file, and can be downloaded from links below. The model was simulated using SBMLsimulator v1.0.