Schematic overview of the stem cell compartment in the bone of cKO mice during steady-state and severe stress. Oxygen levels decrease from sinusoids toward the endosteum (O2 triangle). In cKO mice, hematopoietic cells lack PHD2 and will, irrespective of the oxygen gradient, contain constant levels of HIF1α (HIF1α rectangle). Arc arrow indicates self-renewal capacity. Left: Under steady-state conditions, the absolute number of the PHD2-deficient MPPs is increased due to the sustained HIF1α activity and consequent inhibition of the TGFβ pathway. Right: Under severe stress, induced by irradiation and transplantation of BM or LSK cells, HSCs deficient for PHD2 exhibit enhanced self-renewal. However, PHD2-deficient precursors with a reduced self-renewal capacity (eg, MPP4) were outcompeted by the WT cells and therefore showed decreased chimerism. Abs. num., absolute number; Prolif., proliferation.
