It was not that long ago that cellular differentiation was thought to be a unidirectional process: Cells that became neurons were fated to remain neurons and so forth. However, pioneering research since the first cloned animal Dolly was born in 1996 has shown us that cell fate is not deterministic, and cells can be converted into different states through diverse reprogramming strategies (1). For example, oocyte-mediated reprogramming, using nuclear transfer technology, enables conversion of differentiated cells into totipotent cloned embryos; these embryos can develop into cloned animals in vivo or used to create embryonic stem cells in vitro. Although nuclear transfer embryonic stem cells have been successfully generated using human cells, ethical issues involved in using human oocytes have limited applications in regenerative medicine. One alternative strategy to derive similarly reprogrammed cells is based on the ectopic expression of transcription factors (TFs), 2 such as the four TFs collectively known as the Yamanaka factors, which can induce differentiated cells into pluripotent stem cells (iPSCs) that can be further differentiated into desired cell types in vitro for cell replacement therapies and drug screening. TFs can also be applied to directly convert one type of somatic cells into another. This strategy, called transdifferentiation, can bypass the pluripotent stage, thus avoiding the tumorigenicity arising from acquisition of pluripotency. However, TF-based reprogramming has its own safety concerns, as application of this strategy would require the insertion of retroviral vectors and could potentially reactivate exogenous transcription factors, leading to unintended outcomes. To circumvent these problems, recent efforts have been focused on small molecule compounds, which have been used to convert somatic cells into pluripotent stem cells and other functional differentiated cells (2). Chemical reprogramming has several advantages over other methods, including structural versatility and the comparatively low costs of making the molecules, and the ability to create a highly controlled dosing schedule (2, 3). However, chemical treatments also require a long time course and yield only low efficiency conversions, especially in chemically induced transdifferentiation.To achieve higher conversion rates, a better mechanistic understanding of the reprogramming process is needed. Previous studies have shown that somatic reprogramming induced by Yamanaka factors is a multistep process, in which induction of the mesenchymal-to-epithelial transition (MET) is the initiation step of reprogramming (Fig.