Abstract
Neural crest stem cells (NCSCs) give rise to the neurons and glia of the peripheral nervous system (PNS). NCSC-like cells can be isolated from multiple peripheral organs and maintained in neurosphere culture. Combining in vitro culture and transplantation, we show that expanded embryonic NCSC-like cells lose PNS traits and are reprogrammed to generate CNS cell types. When transplanted into the embryonic or adult mouse CNS, they differentiate predominantly into cells of the oligodendrocyte lineage without any signs of tumor formation. NCSC-derived oligodendrocytes generate CNS myelin and contribute to the repair of the myelin deficiency in shiverer mice. These results demonstrate a reprogramming of PNS progenitors to CNS fates without genetic modification and imply that PNS cells could be a potential source for cell-based CNS therapy.
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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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Brain Injuries / metabolism
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Brain Injuries / physiopathology
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Brain Injuries / surgery*
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Cell Differentiation / 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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Disease Models, Animal
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Embryo, Mammalian
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Female
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Ganglia, Spinal / cytology
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Gene Expression Regulation, Developmental / physiology*
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Glial Fibrillary Acidic Protein / metabolism
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Green Fluorescent Proteins / genetics
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Intercellular Signaling Peptides and Proteins / pharmacology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microtubule-Associated Proteins / metabolism
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Myelin Basic Protein / genetics
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Myelin Basic Protein / metabolism
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Myelin Proteolipid Protein / genetics
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Myelin Proteolipid Protein / metabolism
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Myelin Sheath / metabolism*
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Myelin Sheath / ultrastructure
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Nerve Tissue Proteins / metabolism
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Neural Stem Cells / physiology*
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Neurofilament Proteins / metabolism
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O Antigens / metabolism
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Oligodendrocyte Transcription Factor 2
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Oligodendroglia / physiology*
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Oligodendroglia / ultrastructure
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Stem Cell Transplantation / methods*
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Transfection / methods
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Tubulin / metabolism
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Glial Fibrillary Acidic Protein
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Intercellular Signaling Peptides and Proteins
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Microtubule-Associated Proteins
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Mtap2 protein, mouse
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Myelin Basic Protein
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Myelin Proteolipid Protein
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Nerve Tissue Proteins
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Neurofilament Proteins
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O Antigens
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Olig2 protein, mouse
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Oligodendrocyte Transcription Factor 2
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Plp1 protein, mouse
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Tubulin
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beta3 tubulin, mouse
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enhanced green fluorescent protein
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Green Fluorescent Proteins