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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.. null, 20.
Institute for Systems Theory and Automatic Control, University of Stuttgart, 70550 Stuttgart, Germany. schittler@ist.uni-stuttgart.desteffen.waldherr@ovgu.deInstitute for Automation Engineering, Otto von Guericke University MagdeburgBIOMD0000000493Mesenchymal 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.Cell differentiation modeled via a coupled two-switch regulatory network.Schittler D D, Hasenauer J J, Allgöwer F F, Waldherr S STaf[[II]]250, Taf200, Chondrocyte, dTAF[[II]]230, TAF[[II]]250, d230, dTAF[[II]]250, TAF[[II]]230, TFIID TAF250, cel, cell, FATE, TAF200, l(3)84Ab, dTAFII250, Taf1p, TAF[II]250, BG:DS00004.13, Osteoblast, TAFII-250, CG17603, TAF250/230, TAF[[II]], EfW1, Cell, dTAF230, dTAF250, dmTAF[[II]]230, TAFII250, Chondroblasts, DmelCG17603, Taf250, dmTAF1, SR3-5, Taf230, p230, Chondroblast., CT43, TAF[[II]]250/230, TFIID, TAF, TAF230, TAF250, TAF1projections, Chondrocyte, determination, Success, Stem Cells, Addresses, Stromal Cells, Biochemical, Single-cells, Mesenchymal Stromal Cells, Differentiated., Multipotent Mesenchymal 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Adipose-Derived Mesenchymal Stem Cells, Relational and Item-Specific Encoding Task, Mathematics, Adipose Tissue Derived Mesenchymal Stromal Cells, Modeling, portion of bone tissue, MSI Stable, shelves, RiSE, chondrogenic element, Adipose Tissue Derived Mesenchymal Stem Cells, CG17603, TAF[[II]], projection, ridge, State Ownership, Adipose-Derived Mesenchymal Stromal Cells, Adipose Derived, loss of, organ system, Part Dosing Unit, Chondroblasts, cartilage, Mesenchymal Progenitor Cell, Taf250, bone, spine, SR3-5, Ancestors, Mesenchymal, Adipose Derived Mesenchymal Stromal Cells, Adipose Tissue Derived Mesenchymal Stem Cell, inherited genetic, School-Age Population, Bone Marrow Stromal Cells, E430016J11Rik, TAF230, Provided, cartilage organ, Multipotent Bone Marrow Stromal Cells, Mesenchymal Stem Cell, d230, Cellular Differentiation, Effects, Math, lamellae, Mesenchymal Stem Cells, Different, Progenitor Cell, Adipose Tissue Derived Mesenchymal Stromal Cell, Wharton's Jelly Cells, 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impact-a, dTAF230, US State, p230, Successful, chemical analysis, TAF[[II]]250/230, TFIID, bones, connected anatomical system, flange, organ process, Stimuli, Taf[[II]]250, Bone Marrow Stromal Cell, differentiation, osseous tissue, Biochemical Response, Relational and Item-Specific Encoding (RiSE), TAF[[II]]230, Cell Differentiation Process, Multipotent Bone Marrow Stromal Cell, Adipose Tissue-Derived Mesenchymal Stromal Cell, stem cell, TAF[II]250, Osteoblast, Biochemical Evidence of Disease, School Age Populations, Floor, processes, process, Stimulus, BED-Biochemical Evidence of Disease, Differential, Adipose Tissue-Derived Mesenchymal Stem Cells, mineralized bone tissue, DmelCG17603, Multipotent, processus, calcium tissue, assay, bone organ, Experimental Result, hereditary, RWDD5, Intrinsic, TAF1projections, extent, fs(1)A384, dec, Chondrocyte, Public Sectors, determination, Stem Cells, Addresses, Stromal Cells, Mesenchymal Stromal Cells, Multipotent Mesenchymal Stromal Cell, 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Interface, Switch Device, Consortium or Network., Network Device, Coupled, Switch, Cell Differentiations, Network, Consortium, Switch/Relay, Coupling, Differentiation, Cell, Differentiations, NCI Consortium or NetworkfalseSchittler2010 - Cell fate of progenitor cells, osteoblasts or chondrocytes
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:
Cell differentiation modeled via a coupled two-switch regulatory network.
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.
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2018-12-212013-11-192013-10-15BIOMD000000049321198133MODEL1310150000BIOMD0000000493GO:0048762131567BTO:0000421BTO:0000725BTO:0002050BTO:0005092