Astrocytes derive from the tripotent neural stem cells, which also give rise to neurons and oligodendrocytes. The development of these major cell types of the brain occur sequentially due to various signalling mechanisms and epigenetic regulation, where neurons are initially favoured. Many studies have shown how neural stem cells can be differentiated to astrocytes in vitro, however, most do not recapitulate the oxygen level in gestation, require the use of xenogeneic serum, or take a considerable amount of time. In this study, we show that a short 7-day differentiation in the presence of CNTF and at 5% O2 may promote the gliogenic transition, the first step towards the generation of astrocytes. We further evaluated growth factors that have been individually, or in combination, shown to affect the expression of an astrocyte-specific marker, GFAP, by conducting a factorial experiment with various concentrations of LIF, BMP4, bFGF, and RA. Our results may suggest that only the former two, in addition to CNTF, were required to induce neuronal differentiation, which might then induce gliogenic transition by upregulating NFIA through Notch signalling.
Keywords: human neural stem cell, astrocytes, cell differentiation, oxygen concentration, hypoxia
(C) Dimitri Wirjowerdojo (2018). "Evaluation of Hypoxia-induced Astrocytic Commitment of Neuroepithelial Stem Cells". Master's thesis for Molecular Techniques in Life Science. KTH Royal Institute of Technology, Karolinska Institutet, Stockholm University, and Science for Life Laboratory.
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