title: 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.
authors.affiliation: The Ludwig Institute for Cancer Research, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Stina
authors.initials: S
authors.lastname: Friling
authors.forename: Elisabet
authors.initials: E
authors.lastname: Andersson
authors.forename: Lachlan H
authors.initials: LH
authors.lastname: Thompson
authors.forename: Marie E
authors.initials: ME
authors.lastname: Jönsson
authors.forename: Josephine B
authors.initials: JB
authors.lastname: Hebsgaard
authors.forename: Evanthia
authors.initials: E
authors.lastname: Nanou
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Alekseenko
authors.forename: Ulrika
authors.initials: U
authors.lastname: Marklund
authors.forename: Susanna
authors.initials: S
authors.lastname: Kjellander
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Volakakis
authors.forename: Outi
authors.initials: O
authors.lastname: Hovatta
authors.forename: Abdeljabbar
authors.initials: A
authors.lastname: El Manira
authors.forename: Anders
authors.initials: A
authors.lastname: Björklund
authors.forename: Thomas
authors.initials: T
authors.lastname: Perlmann
authors.forename: Johan
authors.initials: J
authors.lastname: Ericson
mesh_terms: 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
chemical_list: D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489692:Lmx1a protein, mouse; D014157:Transcription Factors; D004298:Dopamine