Following a breakthrough that was made in 2006 (by Takahashi & Yamanaka), today we can reverse cellular differentiation, and generate induced pluripotent stem cells from somatic cells by epigenetic “reprogramming”. We investigate what are the dramatic molecular changes happening in the cell during reprogramming and how they are connected to similar in-vivo processes. We pointed out two chromatin regulators that play a role in this process, one is essential for reprogramming (Utx, Mansour et al 2012), and the other (Mbd3/NuRD, Rais et al 2013) is an obstacle, which upon its near-removal the reprogramming becomes dramatically faster and synchronized. Later we have shown that the molecular axis Gatad2a-Chd4-Mbd3 which is part of Mbd3/NuRD complex, is critical for blocking reestablishment of naive pluripotency (Mor et al, 2018). Removal/Repression of components of this complex, brings to high cellular reprogramming efficiency.