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Mol Neurodegener. 2016 Oct 6;11(1):68.

Spinal cord injury induces astroglial conversion towards neuronal lineage.

Author information

1
University of Montpellier, Montpellier, F-34095, France.
2
INSERM U1198, Place Eugène Bataillon CC105, 34095, Montpellier, Cedex 5, France.
3
EPHE, Paris, F-75014, France.
4
INSERM U1051, F-34095, Montpellier, France.
5
Integrative Biology of Neurodegeneration", IKERBASQUE Basque Foundation for Science and Neuroscience Department, University of the Basque Country, E-48013, Bilbao, Spain.
6
Department of Neurosurgery, Gui de Chauliac Hospital, F-34295, Montpellier, France.
7
University of Montpellier, Montpellier, F-34095, France. florence.perrin@inserm.fr.
8
INSERM U1198, Place Eugène Bataillon CC105, 34095, Montpellier, Cedex 5, France. florence.perrin@inserm.fr.
9
EPHE, Paris, F-75014, France. florence.perrin@inserm.fr.
10
INSERM U1051, F-34095, Montpellier, France. florence.perrin@inserm.fr.
11
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.

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 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

PMID:
27716282
PMCID:
PMC5052929
DOI:
10.1186/s13024-016-0133-0
[Indexed for MEDLINE]
Free PMC Article

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