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Induced pluripotent stem cells (iPSC) are generated by reprogramming differentiated somatic cells to a pluripotent cell state that highly resembles embryonic stem cells (ESC) [1]. Fully reprogrammed iPSC can differentiate into any adult cell type [2-6]. Takahashi and Yamanaka generated the first iPSC in 2006 by transfecting fibroblasts with four defined factors: SOX2, OCT4, KLF4, c-MYC (SOKM; also referred to as Yamanaka factors) [7]. The clinical use of iPSC offers great potential for regenerative medicine as any cell type can be generated from true pluripotent cells [8-10]. However, human clinical iPSC applications are currently limited by inefficient methods of reprogramming that often generate incompletely reprogrammed pluripotent states that harbor potentially cancerous epigenetic signatures, and possess limited or skewed differentiation capacities [11-13]. Many standard iPSC lines do not fully resemble pluripotent ESC, and often retain an epigenetic memory of their cell of origin [14, 15]. Such incompletely reprogrammed iPSC also display limited differentiation potential to all three germ layers (e.g., endoderm, ectoderm, mesoderm) [16, 17].

The Role of an NFκB-STAT3 Signaling Axis in Regulating the Induction and Maintenance of the Pluripotent State