Gene Expression Changes in the Course of Neural Progenitor Cell Differentiation

The molecular changes underlying neural progenitor differentiation are essentially unknown. We applied cDNA microarrays with 13,627 clones to measure dynamic gene expression changes during the in vitro differentiation of neural progenitor cells that were isolated from the subventricular zone of post...

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Bibliographic Details
Published in:The Journal of neuroscience 2004-06, Vol.24 (26), p.5982-6002
Main Authors: Gurok, Ulf, Steinhoff, Christine, Lipkowitz, Bettina, Ropers, H.-Hilger, Scharff, Constance, Nuber, Ulrike A
Format: Article
Language:English
Subjects:
Animals
Brain-Derived Neurotrophic Factor - pharmacology
Cell Differentiation - drug effects
Cell Differentiation - genetics
Cell Division
Cells, Cultured - cytology
Cells, Cultured - drug effects
Cells, Cultured - metabolism
Cellular/Molecular
Cytoskeletal Proteins - biosynthesis
Cytoskeletal Proteins - genetics
DNA, Complementary - genetics
Gene Expression Profiling
Gene Expression Regulation, Developmental - drug effects
Lateral Ventricles - cytology
Lateral Ventricles - growth & development
Lateral Ventricles - metabolism
Mice
Nerve Growth Factors - pharmacology
Nerve Tissue Proteins - biosynthesis
Nerve Tissue Proteins - genetics
Neurons - cytology
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Spheroids, Cellular - metabolism
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
Transcription Factors - biosynthesis
Transcription Factors - genetics
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Summary:The molecular changes underlying neural progenitor differentiation are essentially unknown. We applied cDNA microarrays with 13,627 clones to measure dynamic gene expression changes during the in vitro differentiation of neural progenitor cells that were isolated from the subventricular zone of postnatal day 7 mice and grown in vitro as neurospheres. In two experimental series in which we withdrew epidermal growth factor and added the neurotrophins Neurotrophin-4 or BDNF, four time points were investigated: undifferentiated cells grown as neurospheres, and cells 24, 48, and 96 hr after differentiation. Expression changes of selected genes were confirmed by semiquantitative RT-PCR. Ten different groups of gene expression dynamics obtained by cluster analysis are described. To correlate selected gene expression changes to the localization of respective proteins, we performed immunostainings of cultured neurospheres and of brain sections from adult mice. Our results provide new insights into the genetic program of neural progenitor differentiation and give strong hints to as yet unknown cellular communications within the adult subventricular zone stem cell niche.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.0809-04.2004