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Direct conversion of human fibroblasts to dopaminergic neurons
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Direct conversion of human fibroblasts to dopaminergic neurons
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Journal Article
Direct conversion of human fibroblasts to dopaminergic neurons
2011
Overview
Recent reports demonstrate that somatic mouse cells can be directly converted to other mature cell types by using combined expression 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 functional neurons. We also demonstrate that the converted neurons can be directed toward distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided together with the three conversion factors. By combining expression of 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 neurons derived from human somatic cells could be valuable for disease modeling and cell replacement therapy.
Publisher
National Academy of Sciences Issue,National Acad Sciences,National Academy of Sciences
Subject
/ Action Potentials - physiology
/ Animals
/ Cell Transdifferentiation - physiology
/ Cells
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Dopamine
/ Embryos
/ Genes
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Humans
/ Induced pluripotent stem cells
/ Medicinska och farmaceutiska grundvetenskaper
/ Mice
/ Neurons
/ POU Domain Factors - genetics
/ POU Domain Factors - metabolism
/ Rodents
