A mathematical modeling framework to simulate and analyze cell type transitions
Daniella Schittler
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Daniella Schittler, A mathematical modeling framework to simulate and analyze cell type transitions (2015), Logos Verlag, Berlin, ISBN: 9783832587437
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Beschreibung / Abstract
The quantitative understanding of changes in cell types, referred to as cell type transitions, is fundamental to advance fields such as stem cell research, immunology, and cancer therapies.
This thesis provides a mathematical modeling framework to simulate and analyze cell type transitions. The novel methodological approaches and models presented here address diverse levels which are essential in this context:
Gene regulatory network models represent the cell type-determining gene expression dynamics. Here, a novel construction method for gene regulatory network models is introduced, which allows to transfer results from generic low-dimensional to realistic high-dimensional gene regulatory network models.
For populations of cells, a generalized model class is proposed that accounts for multiple cell types, division numbers, and the full label distribution. Analysis and solution methods are presented for this new model class, which cover common cell population experiments and allow to exploit the full information from data.
The modeling and analysis methods presented here connect formerly isolated approaches, and thereby contribute to a holistic framework for the quantitative understanding of cell type transitions.
This thesis provides a mathematical modeling framework to simulate and analyze cell type transitions. The novel methodological approaches and models presented here address diverse levels which are essential in this context:
Gene regulatory network models represent the cell type-determining gene expression dynamics. Here, a novel construction method for gene regulatory network models is introduced, which allows to transfer results from generic low-dimensional to realistic high-dimensional gene regulatory network models.
For populations of cells, a generalized model class is proposed that accounts for multiple cell types, division numbers, and the full label distribution. Analysis and solution methods are presented for this new model class, which cover common cell population experiments and allow to exploit the full information from data.
The modeling and analysis methods presented here connect formerly isolated approaches, and thereby contribute to a holistic framework for the quantitative understanding of cell type transitions.
Inhaltsverzeichnis
- BEGINN
- 1 Introduction
- 1.1 Research motivation
- 1.2 Overview on the research topic
- 1.3 Contribution of this thesis
- 1.4 Outline of this thesis
- 2 Modeling and analysis of a gene switch determining cell differentiation
- 2.1 Background and problem formulation
- 2.2 A gene switch model for cell differentiation
- 2.3 Stochastic dynamics on cell population level
- 2.4 Summary and discussion
- 3 Construction of multistability-equivalent gene regulatory network models
- 3.1 Background and problem formulation
- 3.2 Construction method
- 3.3 Example: Mesenchymal stem cell differentiation
- 3.4 Summary and discussion
- 4 A general model class for proliferating multi-cell type populations in labeling experiments
- 4.1 Background and problem formulation
- 4.2 Development and analysis of a general model class
- 4.3 Relationship to other models and model classes
- 4.4 Summary and discussion
- 5 Modeling of CFSE-labeled multi-cell type populations
- 5.1 Background and problem formulation
- 5.2 Specific model for CFSE-labeled multi-cell type populations
- 5.3 Example: CFSE-labeled stem cell population
- 5.4 Summary and discussion
- 6 Modeling of BrdU-labeled multi-cell type populations
- 6.1 Background and problem formulation
- 6.2 Specific model for BrdU-labeled multi-cell type populations
- 6.3 Examples: Model-based studies on BrdU labeling
- 6.4 Summary and discussion
- 7 Conclusions
- 7.1 Summary and discussion
- 7.2 Outlook
- Appendix
- Bibliography