Abstract
BackgroundHypoxia plays a critical role in various cellular mechanisms, including proliferation and differentiation of neural stem and progenitor cells. In the present study, we explored the impact of lowered oxygen on the differentiation potential of human neural progenitor cells, and the role of erythropoietin in the differentiation process.ResultsIn this study we demonstrate that differentiation of human fetal neural progenitor cells under hypoxic conditions results in an increased neurogenesis. In addition, expansion and proliferation under lowered oxygen conditions also increased neuronal differentiation, although proliferation rates were not altered compared to normoxic conditions. Erythropoietin partially mimicked these hypoxic effects, as shown by an increase of the metabolic activity during differentiation and protection of differentiated cells from apoptosis.ConclusionThese results provide evidence that hypoxia promotes the differentiation of human fetal neural progenitor cells, and identifies the involvement of erythropoietin during differentiation as well as different cellular mechanisms underlying the induction of differentiation mediated by lowered oxygen levels.
Highlights
Hypoxia plays a critical role in various cellular mechanisms, including proliferation and differentiation of neural stem and progenitor cells
The quantification of the data showed that the signal intensity is identical in all conditions tested, with no significant differences in the erythropoietin receptor (EpoR) expression levels (Figure 2B), indicating that level of 20%, EPO did not enhance cell proliferation of hNPCs compared to control cells (Figure 3A)
Lowered oxygen promotes neuronal differentiation of neural progenitor cells (NPC) we investigated the effect of lowered oxygen on the neuronal differentiation of human NPCs
Summary
Hypoxia plays a critical role in various cellular mechanisms, including proliferation and differentiation of neural stem and progenitor cells. We explored the impact of lowered oxygen on the differentiation potential of human neural progenitor cells, and the role of erythropoietin in the differentiation process. Studies of neural stem and progenitor cells play a very important role to understand the mechanisms of differentiation of the cells into lineage specific cells like neurons and astroglia [1]. Within the last few years more attention has been given to micro-environmental oxygen levels for optimized culturing of specific cell types, and for studying the influences of hypoxia and its underlying cellular mechanisms on growth and differentiation of stem cells [3]. We demonstrated a complex network of reactions of human NPC towards hypoxia and propose a mechanism of action within this model
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