Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells.
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.
Friling
Stina
S
The Ludwig Institute for Cancer Research, Karolinska Institutet, 17177 Stockholm, Sweden.
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
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology* / Q000637:transplantation; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008636:Mesencephalon / Q000166:cytology*; D051379:Mice; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D010300:Parkinson Disease / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489692:Lmx1a protein, mouse; D014157:Transcription Factors; D004298:Dopamine