Small molecules enable highly efficient neuronal conversion of human fibroblasts

Forced expression of proneural transcription factors has been shown to direct neuronal conversion of fibroblasts. Because neurons are postmitotic, conversion efficiencies are an important parameter for this process. We present a minimalist approach combining two-factor neuronal programming with small molecule-based inhibition of glycogen synthase kinase-3 beta and SMAD signaling, which converts postnatal human fibroblasts into functional neuron-like cells with yields up to >200% and neuronal purities up to >80%.