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The pioneering landmark, established by Takahashi and Yamanaka (Takahashi et al., 2007; Takahashi and Yamanaka, 2006) in reprogramming somatic cells into induced pluripotent stem (iPS) cells using the four transcriptional factors of Oct4, Sox2, Klf4, and c-Myc, represents one of the most important paradigm shifts in current stem cell biology. This unprecedented discovery could potentially revolutionize regenerative medicine, cell-based therapy and personalized medicine. Despite recent great advancement in cell reprogramming, there are still considerable technical challenges to circumvent restrictions of applications of reprogram‐ ming technology (Kawamura et al., 2009; Saha and Jaenisch, 2009). The utilization of overexpressed transcriptional factors, which of many play oncogenic roles, during somatic reprogramming posts the risk of malignant transformation, thus, limiting its clinical applica‐ tions. Moreover, the reprogramming process using these factors is still inefficient in some of cell types, and is not always successful in other kinds of cells (Kawamura et al., 2009; Marion et al., 2009; Menendez et al., 2012). Therefore, the underlying mechanisms for signaling control of these factors still need to be further explored.

Roles of Tumor Suppressor Signaling on Reprogramming and Stemness Transition in Somatic Cells