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Direct conversion of human fibroblasts to dopaminergic neurons.

Pfisterer, Ulrich LU ; Kirkeby, Agnete LU ; Torper, Olof LU ; Wood, James LU ; Nelander Wahlestedt, Jenny LU ; Dufour, Audrey; Björklund, Anders LU ; Lindvall, Olle LU ; Jakobsson, Johan LU and Parmar, Malin LU (2011) In Proceedings of the National Academy of Sciences 108(25). p.10343-10348
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,... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
108
issue
25
pages
10343 - 10348
publisher
National Acad Sciences
external identifiers
  • wos:000291857500063
  • pmid:21646515
  • scopus:79959951387
ISSN
1091-6490
DOI
10.1073/pnas.1105135108
language
English
LU publication?
yes
id
93b45bd9-f506-40b5-a20b-5adad86564b8 (old id 2008394)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21646515?dopt=Abstract
date added to LUP
2011-07-04 12:16:46
date last changed
2017-11-12 04:06:31
@article{93b45bd9-f506-40b5-a20b-5adad86564b8,
  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.},
  author       = {Pfisterer, Ulrich and Kirkeby, Agnete and Torper, Olof and Wood, James and Nelander Wahlestedt, Jenny and Dufour, Audrey and Björklund, Anders and Lindvall, Olle and Jakobsson, Johan and Parmar, Malin},
  issn         = {1091-6490},
  language     = {eng},
  number       = {25},
  pages        = {10343--10348},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Direct conversion of human fibroblasts to dopaminergic neurons.},
  url          = {http://dx.doi.org/10.1073/pnas.1105135108},
  volume       = {108},
  year         = {2011},
}