Presented at ACoP14. The differentiation of mammalian hematopoietic stem cells (HSCs) is complex and multiscale, providing an opportunity for mathematical modeling and simulation to aid in mechanistic understanding, and ultimately, to inform drug development efforts. Historically, HSC mathematical models were focused on the development of a subset of cells, but mathematical models encompassing the overall cellular system’s complexity are rarely available. Here, an integrated quantitative systems pharmacology (QSP) model that characterizes multi-organ HSC differentiation was developed by integrating literature models and adding novel features.