Spinal cord injury induces astroglial conversion towards neuronal lineage

Mol Neurodegener. 2016 Oct 6;11(1):68. doi: 10.1186/s13024-016-0133-0.


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.

Keywords: Astrocytes; Astrogliosis; Cell specific transcriptomic; Spinal cord injury; Transdifferentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Astrocytes / metabolism*
  • Cell Lineage*
  • Cell Proliferation / physiology
  • Cell Transdifferentiation / physiology*
  • Cells, Cultured
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • Mice
  • Microglia / cytology*
  • Neural Stem Cells / cytology*
  • Spinal Cord Injuries / metabolism*


  • Glial Fibrillary Acidic Protein