Schematic showing the molecular and cellular effects of ambient air and physioxia on HSCs. In air, α-KG levels and Tet2 activity are relatively increased in HSCs, producing increased conversion of 5-mC to 5-hmC, coupled with HSC differentiation and HSC loss. In physioxia, α-KG levels and Tet2 activity are decreased, which decreases HSC differentiation and increases HSC self-renewal. Illustration by Bryanna C. Reinhardt, Louisiana State University School of Medicine; images/shapes used from BioRender.com.