Recent breakthroughs in using viral transduction of a few genes for the reprogramming of both mouse and human somatic cells into induced pluripotent stem (iPS) cells have opened up tremendous opportunities for the stem cell field (Maherali et al., 2007, Meissner et al., 2007, Nakagawa et al., 2008, Okita et al., 2007, Takahashi et al., 2007, Takahashi and Yamanaka, 2006, Wernig et al., 2007, Wernig et al., 2008, Yu et al., 2007). For the iPS cell approach to be clinically relevant, several challenges remain to be addressed, including the elimination of the risks and drawbacks associated with the current iPS cell method, such as the use of genetic manipulation and the low efficiency and slow kinetics of induction. Recent studies have shown that c-Myc, one of the four genes originally thought to be required for iPS cell generation, is dispensable, but in its absence the reprogramming efficiency is reduced (Nakagawa et al., 2008, Wernig et al., 2008). Here, we have explored two approaches toward identifying conditions that can replace viral transduction of oncogenic transcription factors (TFs) and enhance reprogramming efficiency. In one, we have found that neural progenitor cells can be reprogrammed with fewer genetic manipulations than previously reported somatic cells, and in the other we have found that small molecules may be able to replace viral integration of certain transcription factors and promote the reprogramming process.
