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Mathematical models of budding yeast colony formation and damage segregation in stem cells

Wang, Yanli
http://rave.ohiolink.edu/etdc/view?acc_num=osu1500544727569612

Abstract Details

2017, Doctor of Philosophy, Ohio State University, Mathematics.
This dissertation consists of two chapters. In Chapter 1, we present an individual-based model to study budding yeast colony development. Budding yeast, which undergoes polarized growth during budding and mating, has been a useful model system to study cell polarization. Bud sites are selected differently in haploid and diploid yeast cells: haploid cells bud in an axial manner, while diploid cells bud in a bipolar manner. While previous studies have been focused on the molecular details of the bud site selection and polarity establishment, not much is known about how different budding patterns give rise to different functions at the population level. In this chapter, we developed a two-dimensional agent-based model to study budding yeast colonies with cell-type specific biological processes, such as budding, mating, mating type switch, consumption of nutrients, and cell death. The model demonstrates that the axial budding pattern enhances mating probability at the early stage and the bipolar budding pattern improves colony development under nutrient limitation. Our results suggest that the frequency of mating type switch might control the trade-off between diploidization and inbreeding. The effect of aging was also studied through our model. Based on the simulations, colonies initiated by an aged haploid cell show declined mating probability in the early stage and recover as the rejuvenated offsprings become the majority. But colonies initiated by aged diploid cells do not show disadvantage in colony expansion due to the fact that young cells contribute the most to colony expansion. In Chapter 2, we present a continuous model of transport type to study stem cell aging. Persistent division leads to stem cells suffering from the accumulation of molecular damages, which are commonly recognized as drivers of aging. As research on stem cells continues to advance, interesting questions arise as rapidly as new discoveries. How do stem cells respond to internal and external signals and regulate self-renewal and differentiation? How do stem cells cope with damage accumulation and maintain fitness? In this research, we proposed a novel model to integrate stem cell proliferation and differentiation with damage accumulation in aging process. A system of two structured PDEs are used to model stem cells and TD cells. It is assumed that cell cycle progression is continuous while division is discrete, and damage segregation takes place at division. Regulations from TD cells and stem cells populations are incorporated through negative feedbacks on stem cell proliferation and symmetric division. Aging effect is added through the inhibition from damage accumulation on stem cell proliferation and self-renewal. Our simulations suggest that equal distribution of damage between stem cells and less damage retention in asymmetric division reduce the death rate of stem cells and increase TD cell populations. But asymmetric damage segregation in stem cells leads to less concentrated population density, which may be more stable to sudden increase of damage. Compared to feedbacks solely from TD cells, adding feedbacks from stem cells reduces oscillations and population overshooting when population converges to steady state and shifts the population density to low damage region.
Ching-Shan Chou (Advisor)
Janet Best (Committee Member)
Ghaith Hiary (Committee Member)
Wing-Cheong Lo (Committee Member)
133 p.
Mathematics
Mathematical models; yeast colony formation; stem cells

Recommended Citations

Citations

  • Wang, Y. (2017). Mathematical models of budding yeast colony formation and damage segregation in stem cells [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1500544727569612

    APA Style (7th edition)

  • Wang, Yanli. Mathematical models of budding yeast colony formation and damage segregation in stem cells. 2017. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1500544727569612.

    MLA Style (8th edition)

  • Wang, Yanli. "Mathematical models of budding yeast colony formation and damage segregation in stem cells." Doctoral dissertation, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1500544727569612

    Chicago Manual of Style (17th edition)

osu1500544727569612
696
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