The two major limitations of current technologies for generating human neurons outlined above motivated us and others to develop methods for direct conversion of human fibroblasts into induced neurons, referred to as iN cells (Pang et al., 2011; Ambasudhan et al., 2011; Qiang et al., 2011; Pfisterer et al., 2011a and 2011b; Yoo et al., 2011; Caiazzo et al., 2011; Son et al., 2011). Although these efforts were successful and allow rapid production of human iN cells, all of the currently available protocols for generating human iN cells (as opposed to mouse iN cells) suffer from relatively low yields and low efficiency, and are further hampered by the limited availability and renewability of fibroblasts as starting materials. Moreover, the resulting iN cells often exhibited decreased competence for synapse formation. Specifically, we (Pang et al., 2011) and others (Pfisterer et al., 2011; Son et al., 2011) found that the same three transcription factors that convert mouse fibroblasts into iN cells (Brn2, Ascl1, and Myt1L; Vierbuchen et al., 2010) also trans-differentiate human fibroblasts into iN cells when combined with a fourth transcription
