Abstract
Oligodendrocytes generate and maintain myelin, which is essential for axonal function and protection of the mammalian central nervous system. To advance our molecular understanding of differentiation by these cells, we screened libraries of pharmacologically active compounds and identified inducers of differentiation of Oli-neu, a stable cell line of mouse oligodendrocyte precursors (OPCs). We identified four broad classes of inducers, namely, forskolin/cAMP (protein kinase A activators), steroids (glucocorticoids and retinoic acid), ErbB2 inhibitors, and nucleoside analogs, and confirmed the activity of these compounds on rat primary oligodendrocyte precursors and mixed cortical cultures. We also analyzed transcriptional responses in the chemically induced mouse and rat OPC differentiation processes and compared these with earlier studies. We confirm the view that ErbB2 is a natural signaling component that is required for OPC proliferation, whereas ErbB2 inhibition or genetic knockdown results in OPC differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Biomarkers / analysis
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Biomarkers / metabolism
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cell Line
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Cell Proliferation / drug effects*
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / metabolism*
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Colforsin / metabolism
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Colforsin / pharmacology
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Cyclic AMP / metabolism
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Cyclic AMP / pharmacology
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism
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Intercellular Signaling Peptides and Proteins / pharmacology
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Mice
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Oligodendroglia / cytology
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Oligodendroglia / metabolism*
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RNA Interference / physiology
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Rats
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Receptor, ErbB-2 / antagonists & inhibitors
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Receptor, ErbB-2 / deficiency
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Receptor, ErbB-2 / genetics
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Stem Cells / cytology
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Stem Cells / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / pharmacology
Substances
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Biomarkers
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Intercellular Signaling Peptides and Proteins
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Transcription Factors
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Colforsin
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Cyclic AMP
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Erbb2 protein, mouse
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Receptor, ErbB-2