Since the seminal discovery by Yamanaka et al. demonstrating that four transcription factors were capable of inducing nuclear reprogramming to a pluripotent state, a plethora of publications have followed aimed at improving the efficiency, simplicity, and safety of the original methodology that was based on the use of integrating retroviruses. A better understanding of the basic mechanisms behind reprogramming as well as an improvement in tissue culture conditions have allowed for the development of new tools based on different molecular approaches, such as excisable and nonintegrating vectors, RNA, proteins, and small compounds, among others. In most instances, a dynamic interplay exists between each method's efficiency of reprogramming versus overall safety, and these points need to be considered when choosing a particular approach. Regardless, the fast pace at which this field has advanced in recent years attracted many investigators to enter into the induced pluripotent stem cell (iPSC) world and has made the process of nuclear reprogramming and iPSC generation a routine lab technique.
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