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Mathematical models of stem cell differentiation are commonly based upon the concept of subsequent cell fate decisions, each controlled by a gene regulatory network. These networks exhibit a multistable behavior and cause the system to…
Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically-motivated mathematical models for cell differentiation that generically generate oscillations and hence…
The process controlling the diferentiation of stem, or progenitor, cells into one specific functional direction is called lineage specification. An important characteristic of this process is the multi-lineage priming, which requires the…
A blood cell lineage consists of several consecutive developmental stages from the pluri- or multipotent stem cell to a state of terminal differentiation. Despite their importance for human biology, the regulatory pathways and gene networks…
Stem cells can precisely and robustly undergo cellular differentiation and lineage commitment, referred to as stemness. However, how the gene network underlying stemness regulation reliably specifies cell fates is not well understood. To…
To explain the differentiation of stem cells in terms of dynamical systems theory, models of interacting cells with intracellular protein expression dynamics are analyzed and simulated. Simulations were carried out for all possible protein…
In multicellular organisms, several cell states coexist. For determining each cell type, cell-cell interactions are often essential, in addition to intracellular gene expression dynamics. Based on dynamical systems theory, we propose a…
Characterization of the differences between biological and random networks can reveal the design principles that enable the robust realization of crucial biological functions including the establishment of different cell types. Previous…
Gene regulatory networks typically have low in-degrees, whereby any given gene is regulated by few of the genes in the network. They also tend to have broad distributions for the out-degree. What mechanisms might be responsible for these…
Cell differentiation in multicellular organisms is a complex process whose mechanism can be understood by a reductionist approach, in which the individual processes that control the generation of different cell types are identified.…
We study time continuous branching processes with exponentially distributed lifetimes, with two types of cells that proliferate according to binary fission. A range of possible system dynamics are considered, each of which is characterized…
Systemic properties of living cells are the result of molecular dynamics governed by so-called genetic regulatory networks (GRN). These networks capture all possible features of cells and are responsible for the immense levels of adaptation…
Recent developments in synthetic biology, next-generation sequencing, and machine learning provide an unprecedented opportunity to rationally design new disease treatments based on measured responses to gene perturbations and drugs to…
The different cell types in a living organism acquire their identity through the process of cell differentiation in which the multipotent progenitor cells differentiate into distinct cell types. Experimental evidence and analysis of…
Decisions in the cell that lead to its ultimate fate are important for cellular functions such as proliferation, growth, differentiation, development and death. Understanding this decision process is imperative for advancements in the…
Multicellular tissues are the building blocks of many biological systems and organs. These tissues are not static, but dynamically change over time. Even if the overall structure remains the same there is a turnover of cells within the…
A dynamic model for cell differentiation is studied, where cells with internal chemical reaction dynamics interact with each other and replicate. It leads to spontaneous differentiation of cells and determination, as is discussed in the…
The work is devoted to the analysis of cell population dynamics where cells make a choice between differentiation and apoptosis. This choice is based on the values of intracellular proteins whose concentrations are described by a system of…
Cellular response to a perturbation is the result of a dynamic system of biological variables linked in a complex network. A major challenge in drug and disease studies is identifying the key factors of a biological network that are…
The biological processes of cellular decision making and differentiation involve a plethora of signalling pathways and gene regulatory circuits. These networks, in their turn, exhibit a multitude of motifs playing crucial parts in…