In the October 8th issue of Cell Stem Cell, J. K. Ichida et al. from Harvard University reported the results of their high-content chemical screening study to identify small molecules that can replace Sox2 expression for reprogramming somatic cells. The investigators found that a small inhibitor of TGF-β signaling could serve to replace the transgenic factor in forming induced pluripotent stem (iPS) cells. The small molecule inhibitor along with Oct4, c-Myc, and Klf4 gave rise to a stable intermediate cell type. The researchers found that completion of the reprogramming process was carried out by the induction of the transcription factor, Nanog, in the induced cell intermediates.