In this issue of Blood, by integrating mathematical modeling and experimental approaches, Singh et al show how myeloid bias arises from a combination of hematopoietic stem cell (HSC) differentiation and progenitor proliferation biases.¹ Through an elegant synthesis of mouse data at both the cellular and expression levels with mechanistic mathematical models, the authors quantify and compare specific regulatory processes that drive shifts in lineage contributions during hematopoiesis, particularly in the context of inflammation or aging.