Hypoxia niche models for HSPCs. The previous hypoxia niche model proposed that “hypoxic” HSCs reside in poorly perfused endosteal zones with deepest hypoxia at a certain distance from vascular structures and get oxygenated and activated as they approach the proximity of oxygen-rich blood vessels. In the revised model, the BM cavity exhibits an opposite oxygen gradient with the highest pO2 in arteriole-rich endosteal zones and the lowest in deeper areas of the BM. HSPCs and early primitive progenitor cells reside in heterogeneous perivascular niches (perisinusoidal and periarteriolar) and exhibit similar hypoxic profiles irrespective of their positioning in different BM regions.9 Blue cells depict a “hypoxic” state, whereas red cells depict a “normoxic” state. (Adapted and used with permission from Spencer et al.29 )
