Abstract
Spinal cord injury (SCI) leads to irreversible neuronal loss and glial scar formation, which ultimately result in persistent neurological dysfunction. Cellular regeneration could be an ideal approach to replenish the lost cells and repair the damage. However, the adult spinal cord has limited ability to produce new neurons. Here we show that resident astrocytes can be converted to doublecortin (DCX)-positive neuroblasts by a single transcription factor, SOX2, in the injured adult spinal cord. Importantly, these induced neuroblasts can mature into synapse-forming neurons in vivo. Neuronal maturation is further promoted by treatment with a histone deacetylase inhibitor, valproic acid (VPA). The results of this study indicate that in situ reprogramming of endogenous astrocytes to neurons might be a potential strategy for cellular regeneration after SCI.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / cytology
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Astrocytes / metabolism*
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Astrocytes / transplantation
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COS Cells
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Cell Transplantation / methods
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Cells, Cultured
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Chlorocebus aethiops
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Doublecortin Protein
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Female
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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HEK293 Cells
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Humans
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Interleukin Receptor Common gamma Subunit / deficiency
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Interleukin Receptor Common gamma Subunit / genetics
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Lentivirus / genetics
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred NOD
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Mice, Knockout
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Mice, Transgenic
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Microscopy, Fluorescence
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Neurogenesis / genetics
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Neurons / cytology
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Neurons / metabolism*
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SOXB1 Transcription Factors / genetics
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SOXB1 Transcription Factors / metabolism*
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Spinal Cord Injuries / genetics*
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Spinal Cord Injuries / pathology
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Spinal Cord Injuries / surgery
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Transfection / methods
Substances
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Dcx protein, mouse
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Doublecortin Protein
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Il2rg protein, mouse
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Interleukin Receptor Common gamma Subunit
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SOXB1 Transcription Factors
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Green Fluorescent Proteins