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  • Title: Spinal cord injury induces astroglial conversion towards neuronal lineage.
    Author: Noristani HN, Sabourin JC, Boukhaddaoui H, Chan-Seng E, Gerber YN, Perrin FE.
    Journal: Mol Neurodegener; 2016 Oct 06; 11(1):68. PubMed ID: 27716282.
    Abstract:
    BACKGROUND: Neurons have intrinsic capability to regenerate after lesion, though not spontaneously. Spinal cord injury (SCI) causes permanent neurological impairments partly due to formation of a glial scar that is composed of astrocytes and microglia. Astrocytes play both beneficial and detrimental roles on axonal re-growth, however, their precise role after SCI is currently under debate. METHODS: We analyzed molecular changes in astrocytes at multiple stages after two SCI severities using cell-specific transcriptomic analyses. RESULTS: We demonstrate that astrocyte response after injury depends on both time after injury and lesion severity. We then establish that injury induces an autologous astroglial transdifferentiation where over 10 % of astrocytes express classical neuronal progenitor markers including βIII-tubulin and doublecortin with typical immature neuronal morphology. Lineage tracing confirmed that the origin of these astrocytes is resident mature, rather than newly formed astrocytes. Astrocyte-derived neuronal progenitors subsequently express GABAergic, but not glutamatergic-specific markers. Furthermore, we have identified the neural stem cell marker fibroblast growth factor receptor 4 (Fgfr4) as a potential autologous modulator of astrocytic transdifferentiation following SCI. Finally, we establish that astroglial transdifferentiation into neuronal progenitors starts as early as 72 h and continues to a lower degrees up to 6 weeks post-lesion. CONCLUSION: We thus demonstrate for the first time autologous injury-induced astroglial conversion towards neuronal lineage that may represent a therapeutic strategy to replace neuronal loss and improve functional outcomes after central nervous system injury.
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