Inhibiting Mx1⁺ osteolineage cell production of heparan sulfate proteoglycans disrupts HSC interactions within the bone marrow niche, leading to potential clinical applications that include enhancing donor stem cell mobilization in response to granulocyte colony-stimulating factor (G-CSF) and enabling donor stem cells to engraft in the host bone marrow niche without cytotoxic conditioning. Professional illustration by Patrick Lane, ScEYEnce Studios.