Stochastic Modeling of Hematopoietic Stem Cell Dynamics
Year: 2025
Type: preprint
Abstract: The study of hematopoietic stem cell (HSCs) maintenance and differentiation to supply the hematopoietic system presents unique challenges, given the complex regulation of the process and the difficulty in observing cellular interactions in the stem cell niche. Quantitative methods and tools have emerged as valuable mechanisms to address this issue; however, the stochasticity of HSCs presents significant challenges for mathematical modeling, especially when bridging the gap between theoretical models and experimental validation. In this work, we have built a flexible and user-friendly stochastic dynamical and spatial model for long-term HSCs (LT-HSCs) and short-term HSCs (ST-HSCs) that captures experimentally observed cellular variability and heterogeneity. Our model implements the behavior of LT-HSCs and ST-HSCs and predicts their homeostatic dynamics. Furthermore, our model can be modified to explore various biological scenarios, such as stress-induced perturbations mediated by apoptosis, and successfully implement these conditions. Finally, the model incorporates spatial dynamics, simulating cell behavior in a 2D environment by combining Brownian motion with spatially graded parameters. *Summary Statement This study addresses the challenge of characterizing hematopoietic stem cell (HSC) dynamics by developing a flexible, user-friendly stochastic spatial model of long-term and short-term HSCs. The model captures observed cellular variability and heterogeneity, predicts homeostatic dynamics, can be adapted to simulate stress-induced perturbations like apoptosis, and incorporates a spatial component to analyze HSC movement within a bone marrow niche.
Institution: University of South Carolina
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Center for Targeted Therapeutics, CAREER: Multi-Scale Modeling of Biological Gels by Coupling Langevin Equations and Fractional Viscoelastic Constitutive Models, A screen for epigenetic regulators of hematopoiesis reveals a requirement for the Hbo1 complex during hematopoietic stem cell specification, Ing4-deficiency enhances the regenerative capacity of multipotent progenitor cells
OpenAlex ID: W4406901578