Dataset Information

Wodarz2018/1 - simple model

ABSTRACT: The paper describes a basic model of effect of cellular de-differentiation on the dynamics and evolution of tissue and tumor cells. Created by COPASI 4.25 (Build 207) This model is described in the article: Effect of cellular de-differentiation on the dynamics and evolution of tissue and tumor cells in mathematical models with feedback regulation Dominik Wodarz J Theor Biol. 2018 July 07; 448: 86–93 Abstract: Tissues are maintained by adult stem cells that self-renew and also differentiate into functioning tissue cells. Homeostasis is achieved by a set of complex mechanisms that involve regulatory feedback loops. Similarly, tumors are believed to be maintained by a minority population of cancer stem cells, while the bulk of the tumor is made up of more differentiated cells, and there is indication that some of the feedback loops that operate in tissues continue to be functional in tumors. Mathematical models of such tissue hierarchies, including feedback loops, have been analyzed in a variety of different contexts. Apart from stem cells giving rise to differentiated cells, it has also been observed that more differentiated cells can de-differentiate into stem cells, both in healthy tissue and tumors, aspects of which have also been investigated mathematically. This paper analyses the effect of de-differentiation on the basic and evolutionary dynamics of cells in the context of tissue hierarchy models that include negative feedback regulation of the cell populations. The models predict that in the presence of de-differentiation, the fixation probability of a neutral mutant is lower than in its absence. Therefore, if de-differentiation occurs, a mutant with identical parameters compared to the wild-type cell population behaves like a disadvantageous mutant. Similarly, the process of de-differentiation is found to lower the fixation probability of an advantageous mutant. These results indicate that the presence of de- differentiation can lower the rates of tumor initiation and progression in the context of the models considered here. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . 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.

SUBMITTER: Jinghao Men

PROVIDER: BIOMD0000000774 | BioModels | 2019-08-01

REPOSITORIES: BioModels

ACCESS DATA

Publications

Effect of cellular de-differentiation on the dynamics and evolution of tissue and tumor cells in mathematical models with feedback regulation.

Wodarz Dominik D

Journal of theoretical biology 20180330

Tissues are maintained by adult stem cells that self-renew and also differentiate into functioning tissue cells. Homeostasis is achieved by a set of complex mechanisms that involve regulatory feedback loops. Similarly, tumors are believed to be maintained by a minority population of cancer stem cells, while the bulk of the tumor is made up of more differentiated cells, and there is indication that some of the feedback loops that operate in tissues continue to be functional in tumors. Mathematica ...[more]

PMID: 29605227

Similar Datasets

Project description:The paper describes a model of effect of cellular de-differentiation on the dynamics and evolution of tissue and tumor cells. Created by COPASI 4.25 (Build 207) This model is described in the article: Effect of cellular de-differentiation on the dynamics and evolution of tissue and tumor cells in mathematical models with feedback regulation Dominik Wodarz J Theor Biol. 2018 July 07; 448: 86–93 Abstract: Tissues are maintained by adult stem cells that self-renew and also differentiate into functioning tissue cells. Homeostasis is achieved by a set of complex mechanisms that involve regulatory feedback loops. Similarly, tumors are believed to be maintained by a minority population of cancer stem cells, while the bulk of the tumor is made up of more differentiated cells, and there is indication that some of the feedback loops that operate in tissues continue to be functional in tumors. Mathematical models of such tissue hierarchies, including feedback loops, have been analyzed in a variety of different contexts. Apart from stem cells giving rise to differentiated cells, it has also been observed that more differentiated cells can de-differentiate into stem cells, both in healthy tissue and tumors, aspects of which have also been investigated mathematically. This paper analyses the effect of de-differentiation on the basic and evolutionary dynamics of cells in the context of tissue hierarchy models that include negative feedback regulation of the cell populations. The models predict that in the presence of de-differentiation, the fixation probability of a neutral mutant is lower than in its absence. Therefore, if de-differentiation occurs, a mutant with identical parameters compared to the wild-type cell population behaves like a disadvantageous mutant. Similarly, the process of de-differentiation is found to lower the fixation probability of an advantageous mutant. These results indicate that the presence of de- differentiation can lower the rates of tumor initiation and progression in the context of the models considered here. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . 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.

Project 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: 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. This model is hosted on BioModels Database and identified by: BIOMD0000000493 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . 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.

Dataset Information

Wodarz2018/1 - simple model

Publications

Effect of cellular de-differentiation on the dynamics and evolution of tissue and tumor cells in mathematical models with feedback regulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure