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Discussion:

The author demonstrated that cell sorting technology could be utilized to compensate the addition of exogenous signals during early neural induction from PSCs. More importantly, the author showed the distinct effects of prolonged culture and hypoxic conditions on the neural differentiation of ES-NSCs, ie, prolonged culture was involved in the cell fate after neural differentiation, while hypoxic conditions efficiently promoted neural differentiation. In addition, the author suggested that loss of Sox1 expression might contribute to the loss of neurogenic capacity of NSCs due to prolonged culture whereas HIF-1α expression is responsible for upregulation of neural differentiation. Taken together, the author proposed that careful consideration about time and oxygen tension should be taken into account in the in vitro induction of neural cells from PSCs for clinical utilization of PSC-derived neural cells.

Although the results in this dissertation were derived from mouse ES cells, it will be highly likely applicable for human ES cells and iPS cells. In the fields of basic research, the neural cells derived from human iPS cells can be applied for drug discovery of many kinds of neural disease. As a matter of fact, many kinds of disease-specific iPS cell line derived from patients suffering from neural disease have been generated so far. On the other hand, in the fields of clinical application a marker-expressing PSC (eg, Sox1-expressing ES cells) is not appropriate for clinical use of the cells derived from them, and thus the author discussed that another method such as staining of cell-surface molecule should be developed for application in the clinic.