西亚试剂：Direct conversion of human fibroblasts to dopaminergic neur

Direct conversion of human fibroblasts to dopaminergic neurons

Pfisterer, Ulrich; Kirkeby, Agnete; Torper, Olof; Wood, James; Nelander, Jenny; Dufour, Audrey; Bj?rklund, Anders; Lindvall, Olle; Jakobsson, Johan; Parmar, Malin

Recent reports demonstrate that somatic mouse cells can be directly converted to other mature cell types by using combinedexpression of defined factors. Here we show that the same strategy can be applied to human embryonic and postnatal fibroblasts.By overexpression of the transcription factors Ascl1, Brn2, and Myt1l, human fibroblasts were efficiently converted to functionalneurons. We also demonstrate that the converted neurons can be directed toward distinct functional neurotransmitter phenotypeswhen the appropriate transcriptional cues are provided together with the three conversion factors. By combining expressionof the three conversion factors with expression of two genes involved in dopamine neuron generation, Lmx1a and FoxA2, we could direct the phenotype of the converted cells toward dopaminergic neurons. Such subtype-specific induced neuronsderived from human somatic cells could be valuable for disease modeling and cell replacement therapy.

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