Generation and Characterization of Neural Stem Cells Derived from Embryonic Stem Cells using the Default Mechanism

In embryonic stem cells (ESCs) neural differentiation is elicited in the absence of extrinsic signaling in minimal conditions. This ‘default mechanism’ in ESCs produces neural stem cells termed primitive neural stem cells, which can subsequently yield FGF2-dependent definitive neural stem cells (dNSCs). We hypothesized that dNSCs have properties similar to neural stem/progenitor cells derived from the adult brain (aNPCs). The neural differentiation profile of the cell-types was characterized in vitro and in vivo following transplantation into the Shiverer mouse. The dNSCs produced a differentiation profile similar to that of aNPCs and both cell-types produced oligodendrocytes. This is the first demonstration of the in vivo differentiation of neural stem cells, derived from ESCs through the default mechanism, into the oligodendrocyte lineage. We conclude that dNSCs are a similar cell population to aNPCs. The default mechanism is a promising approach to generate neural stem cells and their progeny from pluripotent cell populations.MAS