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Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10343-8. doi: 10.1073/pnas.1105135108. Epub 2011 Jun 6.

Direct conversion of human fibroblasts to dopaminergic neurons.

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  • 1Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, SE-221 84 Lund, Sweden.

Abstract

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.

Comment in

  • Research highlights. [Regen Med. 2011]
PMID:
21646515
[PubMed - indexed for MEDLINE]
PMCID:
PMC3121829
Free PMC Article

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