title: Direct conversion of human fibroblasts to dopaminergic neurons.
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.
authors.affiliation: Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, SE-221 84 Lund, Sweden.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pfisterer
authors.forename: Agnete
authors.initials: A
authors.lastname: Kirkeby
authors.forename: Olof
authors.initials: O
authors.lastname: Torper
authors.forename: James
authors.initials: J
authors.lastname: Wood
authors.forename: Jenny
authors.initials: J
authors.lastname: Nelander
authors.forename: Audrey
authors.initials: A
authors.lastname: Dufour
authors.forename: Anders
authors.initials: A
authors.lastname: Björklund
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
authors.forename: Johan
authors.initials: J
authors.lastname: Jakobsson
authors.forename: Malin
authors.initials: M
authors.lastname: Parmar
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D054338:Cell Transdifferentiation / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D050809:POU Domain Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C078341:MYT1 protein, human; D050809:POU Domain Factors; D014157:Transcription Factors; C085076:transcription factor Brn-2; D004298:Dopamine