Reprogramming of somatic cells to generate induced pluripotent stem cells (iPSCs) has unprecedented potential for regenerative medicine, for cell-based therapies, for modeling human diseases in culture, and for drug discovery. Our study shows that AID (activation-induced deaminase) is a common early regulator not only in cell fusion-based reprogramming but also in reprogramming to iPSCs. We postulate that an identification of such early regulators will not only increase our understanding of the mechanisms underlying reprogramming but also increase the efficiency of iPSC generation.