Direct conversion of human fibroblasts to dopaminergic neurons.

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Sammanfattning

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.
Originalspråkengelska
Sidor (från-till)10343-10348
TidskriftProceedings of the National Academy of Sciences
Volym108
Nummer25
DOI
StatusPublished - 2011

Ämnesklassifikation (UKÄ)

  • Neurologi
  • Medicinska grundvetenskaper
  • Neurovetenskaper

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