In the past funding year we have made much progress in our understanding how the factors that induce the conversion of skin cells to neurons work on the molecular level. One of the factors, the neuronal factor called Ascl1, is able to activate a neuronal program in skin cells even though this neuronal program is shut down in skin cells. This is a highly unique property of such a factor and called “pioneer factor activity”. This finding nicely explains how the neuronal program can be activated in skin cells.
The question remained though, how the skin cell program is downregulated. Obviously, for a successful reprogramming event, the target cell program (in our case the neuronal program) needs to be activated and the donor cell program (in this case the skin cell program) needs to be silenced. It was completely unclear how a skin program can be specifically silenced with neuronal reprogramming factors. We found that another of our reprogramming factors, the neuronal transcription factor called Myt1l, has the exact opposite function of Ascl1: it is mostly acting as a repressor and its main function in this reprogramming is to silence the skin cell program.