Free heme induces defects in SCD murine MSCs and HSCs in a TLR4-dependent manner. Hemolysis of sickle RBCs leads to release of free heme, which drives changes in BM MSCs and HSCs, including upregulation of ROS. These defects can be reversed in vivo or in vitro by targeting oxidative stress (NAC) or TLR4 pathways. ANGT1, angiopoietin 1. Professional illustration by Patrick Lane, ScEYEnce Studios.