Induced pluripotent stem cells (iPSCs) are created by introducing:
Yamanaka reprogramming showed somatic fibroblasts can be reset to pluripotency by ectopic expression of core pluripotency transcription network via retroviral vectors. Oct4 and Sox2 form heterodimer activating Nanog enhancer and auto-regulatory loop, Klf4 co-activates and suppresses p53 apoptosis, c-Myc enhances proliferation and chromatin remodeling facilitating demethylation of Oct4 promoter and reactivation of endogenous pluripotency circuitry. These four factors induce embryonic stem cell-like state expressing alkaline phosphatase, SSEA4, Tra-1-60, able to form teratoma containing three germ layers. Replacement of oncogenic c-Myc with L-Myc or Lin28 improves safety. Combination distinguishes iPSCs from growth factor cocktails and differentiation protocols.
Ref: Takahashi and Yamanaka, Cell 2006, Induction of Pluripotent Stem Cells by OSKM Factors.