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Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells

Friling, Stina; Andersson, Elisabet; Thompson, Lachlan LU ; Jönsson, Marie LU ; Hebsgaard, Josephine LU ; Nanou, Evanthia; Alekseenko, Zhanna; Marklund, Ulrika; Kjellander, Susanna and Volakakis, Nikolaos, et al. (2009) In Proceedings of the National Academy of Sciences 106(18). p.7613-7618
Abstract
Signaling factors involved in CNS development have been used to control the differentiation of embryonic stem cells (ESCs) into mesencephalic dopamine (mesDA) neurons, but tend to generate a limited yield of desired cell type. Here we show that forced expression of Lmx1a, a transcription factor functioning as a determinant of mesDA neurons during embryogenesis, effectively can promote the generation of mesDA neurons from mouse and human ESCs. Under permissive culture conditions, 75%-95% of mouse ESC-derived neurons express molecular and physiological properties characteristic of bona fide mesDA neurons. Similar to primary mesDA neurons, these cells integrate and innervate the striatum of 6-hydroxy dopamine lesioned neonatal rats. Thus, the... (More)
Signaling factors involved in CNS development have been used to control the differentiation of embryonic stem cells (ESCs) into mesencephalic dopamine (mesDA) neurons, but tend to generate a limited yield of desired cell type. Here we show that forced expression of Lmx1a, a transcription factor functioning as a determinant of mesDA neurons during embryogenesis, effectively can promote the generation of mesDA neurons from mouse and human ESCs. Under permissive culture conditions, 75%-95% of mouse ESC-derived neurons express molecular and physiological properties characteristic of bona fide mesDA neurons. Similar to primary mesDA neurons, these cells integrate and innervate the striatum of 6-hydroxy dopamine lesioned neonatal rats. Thus, the enriched generation of functional mesDA neurons by forced expression of Lmx1a may be of future importance in cell replacement therapy of Parkinson disease. (Less)
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Contribution to journal
publication status
published
subject
keywords
Parkinson, neuroscience, intrinsic determinant, magnetic bead sorting, disease, transplantation
in
Proceedings of the National Academy of Sciences
volume
106
issue
18
pages
7613 - 7618
publisher
National Acad Sciences
external identifiers
  • wos:000265783600063
  • scopus:66149085781
ISSN
1091-6490
DOI
10.1073/pnas.0902396106
language
English
LU publication?
yes
id
03561632-4498-4509-a4f9-8894cbb1aa80 (old id 1426303)
date added to LUP
2009-06-30 13:54:37
date last changed
2017-11-05 03:33:10
@article{03561632-4498-4509-a4f9-8894cbb1aa80,
  abstract     = {Signaling factors involved in CNS development have been used to control the differentiation of embryonic stem cells (ESCs) into mesencephalic dopamine (mesDA) neurons, but tend to generate a limited yield of desired cell type. Here we show that forced expression of Lmx1a, a transcription factor functioning as a determinant of mesDA neurons during embryogenesis, effectively can promote the generation of mesDA neurons from mouse and human ESCs. Under permissive culture conditions, 75%-95% of mouse ESC-derived neurons express molecular and physiological properties characteristic of bona fide mesDA neurons. Similar to primary mesDA neurons, these cells integrate and innervate the striatum of 6-hydroxy dopamine lesioned neonatal rats. Thus, the enriched generation of functional mesDA neurons by forced expression of Lmx1a may be of future importance in cell replacement therapy of Parkinson disease.},
  author       = {Friling, Stina and Andersson, Elisabet and Thompson, Lachlan and Jönsson, Marie and Hebsgaard, Josephine and Nanou, Evanthia and Alekseenko, Zhanna and Marklund, Ulrika and Kjellander, Susanna and Volakakis, Nikolaos and Hovatta, Outi and El Manira, Abdeljabbar and Björklund, Anders and Perlmann, Thomas and Ericson, Johan},
  issn         = {1091-6490},
  keyword      = {Parkinson,neuroscience,intrinsic determinant,magnetic bead sorting,disease,transplantation},
  language     = {eng},
  number       = {18},
  pages        = {7613--7618},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells},
  url          = {http://dx.doi.org/10.1073/pnas.0902396106},
  volume       = {106},
  year         = {2009},
}