Spinal cord injury induces astroglial conversion towards neuronal lineage
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...
| Autores: | , , , , , |
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| Tipo de documento: | artigo |
| Data de publicação: | 2016 |
| País: | España |
| Recursos: | Universidad del País Vasco |
| Repositório: | Addi. Archivo Digital para la Docencia y la Investigación |
| OAI Identifier: | oai:addi.ehu.eus:10810/32388 |
| Acesso em linha: | http://hdl.handle.net/10810/32388 |
| Access Level: | Acceso aberto |
| Palavra-chave: | spinal cord injury astrocytes astrogliosis transdifferentiation cell specific transcriptomic in-vivo reactive astrogliosis glial scar microglia brain transcriptome cells mouse model |
| Resumo: | 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 beta III-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 |
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