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...

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Bibliographic Details
Published in:Nature biotechnology 1999-07, Vol.17 (7), p.653-659
Main Authors: Wagner, Joseph, Åkerud, Peter, Castro, Diogo S., Holm, Pontus C., Canals, Josep M., Snyder, Evan Y., Perlmann, Thomas, Arenas, Ernest
Format: Article
Language:English
Subjects:
Agriculture
Animals
Astrocytes - cytology
Astrocytes - metabolism
Bioinformatics
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Cell Differentiation
Cell Line
Chromatography, High Pressure Liquid
Coculture Techniques
Corpus Striatum - cytology
DNA-Binding Proteins
Dopamine - metabolism
dopaminergic neurons
Fundamental and applied biological sciences. Psychology
Health. Pharmaceutical industry
Industrial applications and implications. Economical aspects
Life Sciences
Mesencephalon - cytology
Mesencephalon - metabolism
Mice
Miscellaneous
Neurons - cytology
Neurons - physiology
Neurons - transplantation
Nuclear Receptor Subfamily 4, Group A, Member 2
Nurr1 protein
Parkinson Disease - therapy
Rats
research-article
Stem Cells - physiology
tissue engineering
Transcription Factors - genetics
Transcription Factors - metabolism
Transfection
Transgenes
Tyrosine 3-Monooxygenase - metabolism
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Description
Summary: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 Nurr 1 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.
ISSN:1087-0156
1546-1696
DOI:10.1038/10862