Stem cells are undifferentiated cells, defined by their capability to self-renew and differentiate to give rise to different cells of the body. Neural stem and progenitor cells are a type of multipotent stem cell capable of giving rise to the cells of the mature central nervous system (CNS): neurons, astrocytes and oligodendrocytes. The mechanism by which various factors influence stem fate is of wide interest, as these cells play a key role in development, and have a potential role in repair of CNS injury. I investigated the role of physiologically relevant hypoxic levels as a driving force for the proliferation and differentiation of Neural Stem and Progenitor Cells (NSPCs) into Oligodendrocytes (OLs) as well as increased migration. In most research, cells are cultured at 21% O2, which is significantly higher than what these cells, and other cells of the CNS, are typically exposed to. Physioxia is what could be considered low concentrations of O2 in the external environment, but normal in the body. The O2 level in the human body is tightly regulated; particularly low levels of O2 may positively aid in NSPC differentiation through the regulation of certain genes. One mechanism that may aid in the differentiation process is the involvement of transcription factors that are sensitive to changes in O2 levels. Hypoxic Inducible Factor (HIF) is a transcription factor that plays an integral role in the detection of hypoxia and can induce changes in genes responsible for vascular growth (vascular endothelial growth factor (VEGF)), cell migration (matrix metalloproteinase 2 (MMP2)) or A disintegrin and metalloproteinase with thrombosponfin motifs 1 (ADAMTS-1)) and cell differentiation (platelet-derived growth factor (PDGF)).
This study demonstrates that a low O2 environment can be confirmed through the upregulation of HIF-1a at low levels of physiologically relevant oxygen levels. Furthermore, the upregulation of VEGF at different O2 concentrations alludes to NSPC proliferation, especially at 5% O2. MMP2 upregulation showed that migration of the OL lineage cells is highest at 5% O2. Lastly, differentiation of NSPCs to OPCs seemed to increase when exposed to low levels of O2 and was the highest at 5% O2. Moderate levels of physiologically relevant oxygen levels such as 5% seem to have the optimal effect on NSPC proliferation, differentiation, and migration as gene expression for several of the gene is highest at that O2 concentration.