Summary of the effects of EPO and hypoxia. Potential mechanisms of neuronal differentiation of hNPCs and the influence of hypoxia and EPO. Proliferating cells in normoxia and hypoxia possess the same proliferation rate. Proliferation and differentiation of cells under normoxic conditions leads to an average yield of neurons. However, changing the oxygen tension after proliferation to hypoxia will lead to a higher yield of neurons. Similar results can be obtained by culturing the cells in hypoxic conditions during proliferation, though a subsequent change to normoxia or continuing the cell culture in hypoxia leads to no additional advantage for the hNPCs. We conclude that hypoxia can induce neurogenesis directly during differentiation and also influence the pool of progenitor cells during proliferation. Anti-apoptotic effects of hypoxia also play a major role in the neuroprotective properties of hypoxia. This anti-apoptotic effect as well as the increased metabolic activity can be partially mimicked by EPO.