Human neural stem cells (hNSCs) can differentiate into an oligodendrocyte lineage to facilitate remyelination in patients. Molecular mechanisms underlying oligodendrocyte fate specification remains unknown, hindering the development of efficient methods to generate oligodendrocytes from hNSCs. We have found that Neurobasal-A medium (NB) is capable of inducing hNSCs to oligodendrocyte progenitor cells (OPCs). We identified several signaling molecules are altered after cultivation in NB medium, including Akt, ERK1/2 and c-Src. While sustained activation of Akt and ERK1/2 during both NB induction and subsequent differentiation was required for OPC differentiation, c-Src phosphorylation was increased temporally during the period of NB induction. Both pharmacological inhibition and RNA interference confirmed that a transient elevation of phospho-c-Src is critical for OPC induction. Furthermore, inactivation of c-Src inhibited phosphorylation of Akt and ERK1/2. In summary, we identified a novel and critical role of c-Src in guiding hNSC differentiation to an oligodendrocyte lineage.

人类神经干细胞（hNSC）可以分化为少突胶质细胞谱系，以促进患者的髓鞘再生。少突胶质细胞命运规范的分子机制仍然未知，阻碍了从hNSCs产生少突胶质细胞的有效方法的发展。我们已经发现，Neurobasal-A培养基（NB）能够诱导hNSCs到少突胶质细胞祖细胞（OPCs）。我们确定了几种信号分子在NB培养基中培养后发生了改变，包括Akt，ERK1 / 2和c-Src。虽然在NB诱导和随后的分化过程中Akt和ERK1 / 2的持续活化是OPC分化所必需的，但在NB诱导期间c-Src磷酸化水平随时间增加。药理学抑制和RNA干扰均证实，磷酸化c-Src的瞬时升高对于OPC诱导至关重要。此外，c-Src的失活抑制了Akt和ERK1 / 2的磷酸化。总之，我们确定了c-Src在指导hNSC分化为少突胶质细胞谱系中的新型和关键作用。