Date of Award
Fall 2025
Document Type
Open Access Thesis
Department
Biological Sciences
First Advisor
Katie Kathrein
Second Advisor
Paula Vasquez
Abstract
Hematopoiesis is a highly regulated process controlled by the hematopoietic stem cells (HSCs). In our previous research, we highlighted the important role of Inhibitor of Growth 4 (Ing4) as a crucial regulator of HSCs and the hematopoietic process. We showed that Ing4-deficient HSCs and multipotent progenitor cells (MPPs) exhibited a quiescent phenotype with an active-like transcriptional profile, suggesting a poised for activation state when needed. In this thesis, we explored the role of ribosomal biogenesis, which is the most upregulated pathway in Ing4-deficient cells, and its impact on the proliferation and differentiation of HSCs and MPPs. Our findings revealed that inhibiting ribosomal biogenesis in Ing4 deficient HSCs and MPPs led to significant delay in proliferation and differentiation compared to wild-type (WT) cells, suggesting a vital role of this pathway in maintenance, quiescence, regulation, and proliferation of HSCs. The study of HSCs and their regulation of the hematopoietic system presents unique challenges, especially when trying to avoid disrupting the system itself. Various quantitative methods and tools have emerged to address this issue, such as mathematical modeling, however, modeling HSC stochasticity is challenging, and their implementation from the model to the bench can be difficult. In this thesis, we have built a flexible and user-friendly stochastic dynamical and spatial model for LT-HSCs and ST-HSCs that captures the cellular variability and heterogeneity, experimentally observed, over time. Our model was able to explore the behavior of mice LT-HSCs and ST-HSCs and predicted their homeostatic dynamics. Furthermore, we showed that our model can explore various biological scenarios, such as stress-induced perturbations mediated by apoptosis. Finally, the spatial component of the model offered valuable insights into the stochastic Brownian motion, location and competitiveness of quiescent and active LT-HSCs and ST-HSCs within a two-dimensional bone marrow niche environment. Together, our qualitative and quantitative findings collectively enhanced our understanding of HSC biology.
Rights
© 2025, Carlos Amadeo Alfaro-Quinde
Recommended Citation
Alfaro-Quinde, C. A.(2025). Characterization of the Role of ING4 in Hematopoietic Stem and Multiprogenitor Cells: An Experimental and Computational Approach. (Master's thesis). Retrieved from https://scholarcommons.sc.edu/etd/8588