Abstract
Stem cells in different regions of the nervous system give rise to different types of mature cells. This diversity is assumed to arise in response to local environmental differences, but the contribution of cell-intrinsic differences between stem cells has been unclear. At embryonic day (E)14, neural crest stem cells (NCSCs) undergo primarily neurogenesis in the gut but gliogenesis in nerves. Yet gliogenic and neurogenic factors are expressed in both locations. NCSCs isolated by flow-cytometry from E14 sciatic nerve and gut exhibited heritable, cell-intrinsic differences in their responsiveness to lineage determination factors. Gut NCSCs were more responsive to neurogenic factors, while sciatic nerve NCSCs were more responsive to gliogenic factors. Upon transplantation of uncultured NCSCs into developing peripheral nerves in vivo, sciatic nerve NCSCs gave rise only to glia, while gut NCSCs gave rise primarily to neurons. Thus, cell fate in the nerve was stem cell determined.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins / metabolism
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Bone Morphogenetic Proteins / pharmacology
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Cell Communication / drug effects
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Cell Communication / genetics
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cell Division / drug effects
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Cell Division / genetics
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Cell Lineage / drug effects
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Cell Lineage / physiology*
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Cell Movement / drug effects
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Cell Movement / genetics
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Cells, Cultured
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Clone Cells / drug effects
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Clone Cells / metabolism
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Enteric Nervous System / cytology
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Enteric Nervous System / embryology*
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Enteric Nervous System / metabolism
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Female
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Fetus
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / genetics
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins / metabolism
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Membrane Proteins / pharmacology
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Nerve Growth Factors / metabolism
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Neural Crest / cytology
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Neural Crest / embryology*
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Neural Crest / metabolism
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Neuregulin-1 / metabolism
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Neuregulin-1 / pharmacology
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Neuroglia / cytology
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Neuroglia / drug effects
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Neuroglia / metabolism*
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Pregnancy
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Rats
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Rats, Sprague-Dawley
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Receptor, Nerve Growth Factor / drug effects
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Receptor, Nerve Growth Factor / genetics
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Receptor, Nerve Growth Factor / metabolism
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Sciatic Nerve / cytology
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Sciatic Nerve / embryology*
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Sciatic Nerve / metabolism
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Stem Cells / cytology
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Stem Cells / drug effects
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Stem Cells / metabolism*
Substances
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Bmp4 protein, rat
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Growth Factors
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Neuregulin-1
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Receptor, Nerve Growth Factor
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delta protein