RESUMEN
It has been previously reported that human embryonic fibroblasts and mouse embryonic fibroblasts can be converted into neuronal cells using chemical agents, along with forced expression specific transcriptional factors. However, the materials required for reprogramming in these approaches presents major technical difficulties and safety concerns. The current study investigated whether a cocktail of small molecules can convert human lung fibroblast cells into neurons. The small molecules valproic acid, CHIR99021, DMH1, Repsox, forskolin, Y27632 and SP600125 (VCHRFYS) were used to induce MRC5 cells into neuronal cells in vitro. Neuronal markers were analyzed by immunofluorescence staining. The gene profiles were analyzed by reverse transcriptionquantitative polymerase chain reaction. MRC5 is a human lung fibroblast cell line derived from normal lung tissue of a 14weekold male fetus. The results of the current study demonstrated that MRC5 fibroblasts can be directly converted into neuronal cells using a cocktail of seven small molecules (VCHRFYS), with a yield of ~90% Tuj1positive cells after 7 days of induction. Following a further maturation period, these chemically-induced neurons possessed neuronal morphology and expressed multiple neuronspecific genes. In conclusion, a cocktail of small molecules that can convert fibroblasts MRC5 cells into functional neurons without the exogenous genetic factors was identified, which has the potential to be useful in neurological disease therapy.