Yamanaka factors (OCT4, SOX2, KLF4, c-MYC) (OSKM)

The Yamanaka factors, comprising the transcription factors OCT4 (POU5F1), SOX2, KLF4, and c-MYC (OSKM), are the primary drivers of cellular reprogramming from a somatic state to an induced pluripotent stem cell (iPSC) state (Takahashi & Yamanaka, 2006). These factors function by binding to specific genome-wide DNA regulatory elements, including enhancers and promoters, to orchestrate a global reset of the epigenetic and transcriptional landscape (Soufi et al., 2012). OCT4 and SOX2 are essential for maintaining the pluripotency gene regulatory network, while KLF4 and c-MYC act as pioneer factors and metabolic regulators to facilitate chromatin accessibility (Chronis et al., 2017). In a therapeutic context, these factors are utilized to generate patient-specific cells for regenerative medicine and disease modeling. However, their clinical application is challenged by the risk of tumorigenesis, particularly due to the oncogenic potential of c-MYC and KLF4, and the possibility of incomplete epigenetic resetting (Soucek et al., 2008). Small molecules like Valproic acid or CHIR99021 are frequently employed to modulate the activity of these factors and improve the safety and efficiency of the reprogramming process (Huangfu et al., 2008).

Other names

Pluripotency factorsiPSC factorsOCT4-SOX2-KLF4-MYCYamanaka reprogramming factorsOSKM factors

Induction of pluripotency through the cooperative binding to genome-wide DNA regulatory elements, leading to the transcriptional activation of pluripotency genes and global epigenetic remodeling of chromatin (Takahashi & Yamanaka, 2006; Soufi et al., 2012).