Direct cell reprogramming into induced pluripotent stem cells (iPSCs) is a stochastic process that can be accelerated. The study shows that most somatic cells can eventually become iPSCs when exposed to reprogramming factors like Oct4, Sox2, Klf4, and c-Myc. The process is influenced by cell division rates and the expression of genes such as p53 and p21. Inhibiting p53/p21 or overexpressing Lin28 increases cell division rates, accelerating iPSC formation. Nanog overexpression, however, accelerates reprogramming independently of cell division rates. The study also identifies two modes of accelerating reprogramming: one dependent on cell division rate and another independent. Quantitative analysis reveals that the number of cell divisions is a key factor in epigenetic reprogramming to pluripotency. The research highlights the stochastic nature of reprogramming, where most cells eventually reach the pluripotent state, and the process is not limited to a small subset of "elite" cells. The findings suggest that reprogramming is a continuous stochastic process, with cell division rate and genetic factors playing critical roles in determining the speed and efficiency of the process. The study also demonstrates that different genetic perturbations can influence reprogramming in distinct ways, providing insights into the mechanisms underlying direct reprogramming.Direct cell reprogramming into induced pluripotent stem cells (iPSCs) is a stochastic process that can be accelerated. The study shows that most somatic cells can eventually become iPSCs when exposed to reprogramming factors like Oct4, Sox2, Klf4, and c-Myc. The process is influenced by cell division rates and the expression of genes such as p53 and p21. Inhibiting p53/p21 or overexpressing Lin28 increases cell division rates, accelerating iPSC formation. Nanog overexpression, however, accelerates reprogramming independently of cell division rates. The study also identifies two modes of accelerating reprogramming: one dependent on cell division rate and another independent. Quantitative analysis reveals that the number of cell divisions is a key factor in epigenetic reprogramming to pluripotency. The research highlights the stochastic nature of reprogramming, where most cells eventually reach the pluripotent state, and the process is not limited to a small subset of "elite" cells. The findings suggest that reprogramming is a continuous stochastic process, with cell division rate and genetic factors playing critical roles in determining the speed and efficiency of the process. The study also demonstrates that different genetic perturbations can influence reprogramming in distinct ways, providing insights into the mechanisms underlying direct reprogramming.