Recent advances in cellular reprogramming have opened the door to the generation of patient-specific cells for regenerative medicine and disease modeling (Takahashi and Yamanaka, 2006; Yu et al., 2007; Nakagawa et al., 2008). Apart from OCT4, NANOG, and SOX2, additional transcription factors (TFs) like zinc-finger transcription factor in cerebellum-3 (Zic3) have been shown to play a role in the maintenance of pluripotency (Lim et al., 2007; 2010). Zic3, a member of the GLI superfamily, has been implicated in the maintenance of pluripotency in mouse and human embryonic stem cells (ESCs) by directly controlling the expression of Nanog (Lim et al., 2007; 2010). Zic3 is also an immediate early gene induced by fibroblast growth factor (FGF) signaling during neural specification (Marchal et al., 2009) and, by preventing neuronal differentiation, plays a role in the maintenance of the neural progenitor cell fate (Inoue et al., 2007). These studies demonstrate thus that Zic3 plays important roles in both the maintenance of ESC pluripotency as well as commitment to and the maintenance of neuroprogenitor cells. We hypothesized that co-transduction of Zic3 together with OCT4 (O), SOX2 (S), and KLF4 (K) might lead to improved generation of induced pluripotent stem cells (iPSCs) from human fibroblasts. Because forced expression of SOX17 or SOX7 in human embryonic stem cells (hESCs) creates stable endodermal and primitive endodermal cell fates (Seguin et al., 2008), the alternative outcome of these experiments could be the creation of stable neuroprogenitor lines.