A strategy that greatly improves the efficiency of directly converting postnatal human fibroblasts into neurons is reported in a study this week in Nature Methods.
Mature human skin cells - fibroblasts - can be converted directly into neurons by genetically modifying the cells to express a cocktail of transcription factors. This strategy promises to be very useful for the study of neuronal development, as a means to model neurological diseases and in regenerative medicine. But the process is known to be inefficient, with only a small proportion of cells being converted. Oliver Brustle and Philipp Koch took human fibroblasts from newborns and young children and cultured them with small molecules that are known to play a role in the production of neurons in vivo. They did this in combination with two transcription factors which subsequently increased the efficiency of neuronal conversion more than fifteen times.
The neurons that were created showed normal functional properties of neurons and expressed genes associated with neuronal cell types. Additionally, preliminary findings reported in this work suggest that this method might also increase the efficiency of direct conversion of adult human fibroblasts to neurons, which will make it possible to establish cellular models of age-related diseases as well.