Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes.
The implementation of neural stem cell lines as a source material for brain tissue transplants is currently limited by the ability to induce specific neurochemical phenotypes in these cells. Here, we show that coordinated induction of a ventral mesencephalic dopaminergic phenotype in an immortalized multipotent neural stem cell line can be achieved in vitro. This process requires both the overexpression of the nuclear receptor Nurr1 and factors derived from local type 1 astrocytes. Over 80% of cells obtained by this method demonstrate a phenotype indistinguishable from that of endogenous dopaminergic neurons. Moreover, this procedure yields an unlimited number of cells that can engraft in vivo and that may constitute a useful source material for neuronal replacement in Parkinson's disease.
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
J
J
Wagner
P
P
Akerud
D S
DS
Castro
P C
PC
Holm
J M
JM
Canals
E Y
EY
Snyder
T
T
Perlmann
E
E
Arenas
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000166:cytology; D004268:DNA-Binding Proteins; D004298:Dopamine / Q000378:metabolism*; D008636:Mesencephalon / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010300:Parkinson Disease / Q000628:therapy; D051381:Rats; D013234:Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D019076:Transgenes; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004268:DNA-Binding Proteins; C539883:Nr4a2 protein, mouse; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine