An extensive analysis and introduced variations hint toward possible optimizations of the process that could push the technique closer to clinical applications.
It enables us to investigate, how the temporal progression of the process is regulated. It also explicitly includes the transduction of factors using viral vectors and their silencing in reprogrammed cells, since this is still a standard procedure in somatic cell reprogramming. Based on the model we calculate an epigenetic landscape for probabilities of cell states. Simulation results show good reproduction of experimental observations during reprogramming, despite the simple structure of the model. An extensive analysis and introduced variations hint toward possible optimizations of the process that could push the technique closer to clinical applications. Faster changes in DNA methylation increase the speed of reprogramming at the expense of efficiency, while accelerated chromatin modifications moderately improve efficiency.
Starting with the successful reprogramming of mouse and human fibroblasts to induced pluripotent stem cells (iPS; Takahashi, 2006; Takahashi et al., 2007), modifications of cell types have become extremely important in recent years.
Manipulating the developmental state of cells transitioning from a differentiated to a pluripotent state or – as recently achieved (Vierbuchen et al., 2010) – to distinct differentiated cell types, opens the door for various clinical applications.
While most of the reprogramming experiments today are still based on the viral transduction of the same four Yamanaka transcription factors SOX2, OCT4, KLF4, and cMYC (Takahashi, 2006), alternative techniques have been developed that improve the concept in various ways (Okita et al., 2008; Zhou et al., 2009).