Abstract
Little is known about how neural stem cells are formed initially during development. We investigated whether a default mechanism of neural specification could regulate acquisition of neural stem cell identity directly from embryonic stem (ES) cells. ES cells cultured in defined, low-density conditions readily acquire a neural identity. We characterize a novel primitive neural stem cell as a component of neural lineage specification that is negatively regulated by TGFbeta-related signaling. Primitive neural stem cells have distinct growth factor requirements, express neural precursor markers, generate neurons and glia in vitro, and have neural and non-neural lineage potential in vivo. These results are consistent with a default mechanism for neural fate specification and support a model whereby definitive neural stem cell formation is preceded by a primitive neural stem cell stage during neural lineage commitment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Body Patterning / drug effects
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Body Patterning / physiology*
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cell Lineage / drug effects
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Cell Lineage / physiology*
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Cell Size / genetics
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Cells, Cultured / cytology
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Cells, Cultured / drug effects
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Cells, Cultured / metabolism
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Chimera / embryology
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Chimera / genetics
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Chimera / metabolism
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Culture Media, Serum-Free / pharmacology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Growth Inhibitors / pharmacology
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Growth Substances / deficiency
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Interleukin-6*
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Intermediate Filament Proteins / drug effects
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Intermediate Filament Proteins / metabolism
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Leukemia Inhibitory Factor
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Lymphokines / pharmacology
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Mammals / embryology*
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Mammals / metabolism
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Mice
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Nerve Tissue Proteins*
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Nervous System / cytology
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Nervous System / embryology*
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Nervous System / growth & development*
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Nestin
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Neurons / cytology*
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Neurons / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Smad4 Protein
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Stem Cells / cytology*
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Stem Cells / drug effects
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Stem Cells / metabolism
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transforming Growth Factor beta / drug effects
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Transforming Growth Factor beta / metabolism
Substances
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Culture Media, Serum-Free
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DNA-Binding Proteins
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Growth Inhibitors
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Growth Substances
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Interleukin-6
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Intermediate Filament Proteins
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Leukemia Inhibitory Factor
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Lif protein, mouse
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Lymphokines
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Nerve Tissue Proteins
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Nes protein, mouse
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Nestin
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Smad4 Protein
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Smad4 protein, mouse
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Trans-Activators
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Transforming Growth Factor beta