It will now be of great interest to decipher the molecular mechanism of this fibroblast to neuron conversion. We assume that high expression levels of strong neural cell-fate determining transcription factors can activate salient features of the neuronal transcriptional program. Auto-regulatory feed-back and feed-forward activation of downstream transcriptional regulators could then reinforce the expression of important cell fate determining genes and help to further stabilize the induced transcriptional program. Robust changes in transcriptional activity could also lead to genome-wide adjustments of repressive and active epigenetic features such as DNA methylation, histone modifications, and changes of chromatin remodeling complexes that further stabilize the new transcriptional network. 12,33 It is possible that certain subpopulations of cells are “primed” to respond to these factors, depending on their pre-existing transcriptional or epigenetic states34.
