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

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.

SUBMITTER: Friling S 

PROVIDER: S-EPMC2671325 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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

Friling Stina S   Andersson Elisabet E   Thompson Lachlan H LH   Jönsson Marie E ME   Hebsgaard Josephine B JB   Nanou Evanthia E   Alekseenko Zhanna Z   Marklund Ulrika U   Kjellander Susanna S   Volakakis Nikolaos N   Hovatta Outi O   El Manira Abdeljabbar A   Björklund Anders A   Perlmann Thomas T   Ericson Johan J  

Proceedings of the National Academy of Sciences of the United States of America 20090421 18

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  ...[more]

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