It is surprising that forced expression of a single transcription factor can produce iN cells from human ES and iPS cells, suggesting that this transcription factor alone initiates a specific neuronal differentiation process. Previous experiments showed that in mouse ES cells, expression of single transcription factors facilitates neuronal differentiation (e.g., see Hamada et al., 2006; Kondo et al., 2008; Sugimoto et al., 2009), but the synaptic competence of the resulting neuron-like mouse cells was not assessed. Moreover, obtaining human iN cells has historically been more challenging than obtaining mouse iN cells (Vierbuchen et al., 2010; Pang et al., 2011). It has been reported that forced overexpression of Sox2 alone can convert mouse and human fibroblasts into NPCs (Ring et al., 2012), although our own experiments required additional transcription factors besides Sox2 for generation of NPCs (Lujan et al., 2012).
