Spinal cord injury induces astroglial conversion towards neuronal lineage.
Mol Neurodegener
; 11(1): 68, 2016 10 06.
Article
em En
| MEDLINE
| ID: mdl-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 ßIII-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismos da Medula Espinal
/
Astrócitos
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Microglia
/
Linhagem da Célula
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Transdiferenciação Celular
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Células-Tronco Neurais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Neurodegener
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
França