Skip to Main content Skip to Navigation
Journal articles

Spinal cord injury induces astroglial conversion towards neuronal lineage

Abstract : AbstractBackgroundNeurons 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.MethodsWe analyzed molecular changes in astrocytes at multiple stages after two SCI severities using cell-specific transcriptomic analyses.ResultsWe 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.ConclusionWe 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [28 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01376950
Contributor : Bmc Bmc <>
Submitted on : Thursday, October 6, 2016 - 8:04:11 AM
Last modification on : Tuesday, October 27, 2020 - 1:50:04 PM
Long-term archiving on: : Saturday, January 7, 2017 - 12:35:56 PM

Files

13024_2016_Article_133.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Harun Najib Noristani, Jean Charles Sabourin, Hassan Boukhaddaoui, Emilie Chan-Seng, Yannick Nicolas Gerber, et al.. Spinal cord injury induces astroglial conversion towards neuronal lineage. Molecular Neurodegeneration, BioMed Central, 2016, 11 (1), pp.68. ⟨10.1186/s13024-016-0133-0⟩. ⟨inserm-01376950⟩

Share

Metrics

Record views

284

Files downloads

390