title: Spinal cord injury induces astroglial conversion towards neuronal lineage.
abstract: 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.
  
  
  
  We analyzed molecular changes in astrocytes at multiple stages after two SCI severities using cell-specific transcriptomic analyses.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: University of Montpellier, Montpellier, F-34095, France.|INSERM U1198, Place Eugène Bataillon CC105, 34095, Montpellier, Cedex 5, France.|EPHE, Paris, F-75014, France.|INSERM U1051, F-34095, Montpellier, France.
authors.forename: Harun Najib
authors.initials: HN
authors.lastname: Noristani
authors.affiliation: Integrative Biology of Neurodegeneration", IKERBASQUE Basque Foundation for Science and Neuroscience Department, University of the Basque Country, E-48013, Bilbao, Spain.
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Sabourin
authors.affiliation: INSERM U1051, F-34095, Montpellier, France.
authors.forename: Hassan
authors.initials: H
authors.lastname: Boukhaddaoui
authors.affiliation: Integrative Biology of Neurodegeneration", IKERBASQUE Basque Foundation for Science and Neuroscience Department, University of the Basque Country, E-48013, Bilbao, Spain.|Department of Neurosurgery, Gui de Chauliac Hospital, F-34295, Montpellier, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Chan-Seng
authors.affiliation: University of Montpellier, Montpellier, F-34095, France.|INSERM U1198, Place Eugène Bataillon CC105, 34095, Montpellier, Cedex 5, France.|EPHE, Paris, F-75014, France.|Integrative Biology of Neurodegeneration", IKERBASQUE Basque Foundation for Science and Neuroscience Department, University of the Basque Country, E-48013, Bilbao, Spain.
authors.forename: Yannick Nicolas
authors.initials: YN
authors.lastname: Gerber
authors.affiliation: University of Montpellier, Montpellier, F-34095, France. florence.perrin@inserm.fr.|INSERM U1198, Place Eugène Bataillon CC105, 34095, Montpellier, Cedex 5, France. florence.perrin@inserm.fr.|EPHE, Paris, F-75014, France. florence.perrin@inserm.fr.|INSERM U1051, F-34095, Montpellier, France. florence.perrin@inserm.fr.|Integrative Biology of Neurodegeneration", IKERBASQUE Basque Foundation for Science and Neuroscience Department, University of the Basque Country, E-48013, Bilbao, Spain. florence.perrin@inserm.fr.
authors.forename: Florence Evelyne
authors.initials: FE
authors.lastname: Perrin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D019070:Cell Lineage; D049109:Cell Proliferation / Q000502:physiology; D054338:Cell Transdifferentiation / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology*; D013119:Spinal Cord Injuries / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein
keywords: Astrocytes; Astrogliosis; Cell specific transcriptomic; Spinal cord injury; Transdifferentiation