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 factor (NeuroD1), a process that may be additionally facilitated by co-expression of microRNAs (Yoo et al., 2011; Ambasudhan et al., 2011). However, apart from the limited capabilities of iN cells produced by these procedures, these experiments did not clarify the minimal requirement of defined factors for trans-differentiating human non-neuronal cells into neurons, and suggested that ancillary factors, such as specific culture conditions, may introduce further variability into these trans-differentiation protocols. Together, these features make analysis of disease-related phenotypes using human iN cells difficult, especially since these protocols do not generate large amounts of iN cells that are fully competent to form synapses.
