Abstract
The stem cell microenvironment is involved in regulating the fate of the stem cell with respect to self-renewal, quiescence, and differentiation. Mathematical models are helpful in understanding how key pathways regulate the dynamics of stem cell maintenance and homeostasis. This tight regulation and maintenance of stem cell number is thought to break down during carcinogenesis. As a result, the stem cell niche has become a novel target of cancer therapeutics. Developing a quantitative understanding of the regulatory pathways that guide stem cell behavior will be vital to understanding how these systems change under conditions of stress, inflammation, and cancer initiation. Predictions from mathematical modeling can be used as a clinical tool to guide therapy design. We present a survey of mathematical models used to study stem cell population dynamics and stem cell niche regulation, both in the hematopoietic system and other tissues. Highlighting the quantitative aspects of stem cell biology, we describe compelling questions that can be addressed with modeling. Finally, we discuss experimental systems, most notably Drosophila, that can best be used to validate mathematical predictions.
Highlights
The hematopoietic stem cell niche is an important regulator of stem cell fate
Understanding the biology and dynamics of stem cell behavior under normal conditions and examining how the dynamics change under conditions of stress is essential to our understanding of how these mechanisms might change during carcinogenesis
We present a review of quantitative approaches to understanding stem cell niche signaling in the hematopoietic system, as well as in other tissues under conditions of homeostasis and carcinogenesis
Summary
The hematopoietic stem cell niche is an important regulator of stem cell fate. There are complex signaling pathways, such as Notch, Wnt, and Hedgehog, that carefully regulate stem cell renewal, differentiation, and quiescence [1,2,3]. Mathematical models can be useful in studying the dynamics of stem cell maintenance. Mathematical and physical models have been used to study stem cell population dynamics and the regulation of stem cell fate through niche signaling with great success. We present a review of quantitative approaches to understanding stem cell niche signaling in the hematopoietic system, as well as in other tissues under conditions of homeostasis and carcinogenesis. We explain the benefits of mathematical models in advancing our understanding of the mechanisms of regulation of stem cell fate and how this regulation changes in cancer development. We highlight the synergistic relationship between mathematical predictions and experimental validation and illustrate Drosophila as a model system for quantitative studies of the stem cell niche.
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