Direct conversion of human fibroblasts to dopaminergic neurons

TY - JOUR

T1 - Direct conversion of human fibroblasts to dopaminergic neurons

AU - Pfisterer, Ulrich

AU - Kirkeby, Agnete

AU - Torper, Olof

AU - Wood, James

AU - Nelander, Jenny

AU - Dufour, Audrey

AU - Björklund, Anders

AU - Lindvall, Olle

AU - Jakobsson, Johan

AU - Parmar, Malin

PY - 2011/6/21

Y1 - 2011/6/21

N2 - 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 phenotypeswhen 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 subtypespecific induced neurons derived from human somatic cells could be valuable for disease modeling and cell replacement therapy.

AB - 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 phenotypeswhen 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 subtypespecific induced neurons derived from human somatic cells could be valuable for disease modeling and cell replacement therapy.

UR - http://www.scopus.com/inward/record.url?scp=79959951387&partnerID=8YFLogxK

U2 - 10.1073/pnas.1105135108

DO - 10.1073/pnas.1105135108

M3 - Journal article

C2 - 21646515

AN - SCOPUS:79959951387

SN - 0027-8424

VL - 108

SP - 10343

EP - 10348

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 25

ER -